Dr Irina Redchenko

Research Area: Immunology
Scientific Themes: Cancer Biology

My research has been focused on tumour immunology and immunotherapy. I’ve been working in both academia and industry on pre-clinical and clinical development of cancer vaccines. Recently, I’ve joined the Jenner Institute to initiate a Cancer Vaccine Programme. Cancer vaccines face the challenge of breaking immunological tolerance to self-antigens that often are the only targets available for vaccine-targeted immune response. A heterologous viral vectored vaccination platform developed by the Jenner researches has proved to be highly efficient in an induction of potent poly-functional protective immune responses against infectious agents. The CD8+ T cells play an essential if not major role in tumour immunosurveillance also. If a strong T cell immune response can be elicited against self-antigens expressed in tumours, it can be tumour-protective. My objective is to adapt and optimize this heterologous prime boost vaccination regime in a cancer setting using a prostate tumour model. The successful delivery of this project may lead to its translation into the clinic.

There are no collaborations listed for this principal investigator.

Cappuccini F, Pollock E, Stribbling S, Hill AVS, Redchenko I. 2017. 5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy. Oncotarget, 8 (29), pp. 47474-47489. | Show Abstract | Read more

The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells. By comparison, homologous MVA vaccination regimen did not induce detectable 5T4-specific T cell responses. ChAdOx1-MVA vaccinated mice were completely protected against subsequent B16 melanoma challenge, but in therapeutic settings this regime was only modestly effective in delaying tumour outgrowth. Concomitant delivery of the vaccine with monoclonal antibodies (mAbs) targeting immune checkpoint regulators LAG-3, PD-1 or PD-L1 demonstrated that the combination of vaccine with anti PD-1 mAb could significantly delay tumour growth and increase overall survival of tumour-bearing mice. Our findings support a translation of the combinatorial approach based on the heterologous ChAdOx1-MVA vaccination platform with immune checkpoint blockade into the clinic for the treatment of 5T4-positive tumours such as prostate, renal, colorectal, gastric, ovarian, lung cancer and mesothelioma.

Romero P, Banchereau J, Bhardwaj N, Cockett M, Disis ML, Dranoff G, Gilboa E, Hammond SA, Hershberg R, Korman AJ et al. 2016. The Human Vaccines Project: A roadmap for cancer vaccine development. Sci Transl Med, 8 (334), pp. 334ps9. | Show Abstract | Read more

Cancer vaccine development has been vigorously pursued for 40 years. Immunity to tumor antigens can be elicited by most vaccines tested, but their clinical efficacy remains modest. We argue that a concerted international effort is necessary to understand the human antitumor immune response and achieve clinically effective cancer vaccines.

Cappuccini F, Stribbling S, Pollock E, Hill AVS, Redchenko I. 2016. Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer. Cancer Immunol Immunother, 65 (6), pp. 701-713. | Show Abstract | Read more

Prostate cancer possesses several characteristics that make it a suitable candidate for immunotherapy; however, prostate cancer vaccines to date demonstrate modest efficacy and low immunogenicity. The goal of the present pre-clinical study was to explore the immunogenic properties and protective efficacy of a novel prostate cancer immunotherapy based on the heterologous prime-boost viral-vectored vaccination platform. The simian adenovirus, ChAdOx1, and modified vaccinia Ankara virus, MVA, encoding a prostate cancer-associated antigen, the six transmembrane epithelial antigen of the prostate 1 (STEAP1), induced strong sustained antigen-specific CD8+ T-cell responses in C57BL/6 and BALB/c male mice. Unexpectedly, the high vaccine immunogenicity translated into relatively low protective efficacy in the murine transplantable and spontaneous models of prostate cancer. A combination of the vaccine with PD-1 blocking antibody significantly improved survival of the animals, with 80 % of mice remaining tumour-free. These results indicate that the ChAdOx1-MVA vaccination regime targeting STEAP1 combined with PD-1 therapy might have high therapeutic potential in the clinic.

Harrop R, Drury N, Shingler W, Chikoti P, Redchenko I, Carroll MW, Kingsman SM, Naylor S, Griffiths R, Steven N, Hawkins RE. 2008. Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses. Cancer Immunol Immunother, 57 (7), pp. 977-986. | Show Abstract | Read more

Modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax) has been evaluated in an open label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during and after treatment with 5-fluorouracil, leukovorin and irinotecan. TroVax was administered to 19 patients with metastatic colorectal cancer. Twelve patients had blood samples taken following each of the six injections and were considered to be evaluable for assessment of immunological responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector MVA were monitored throughout the study. Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity. Of the 12 patients who were evaluable for assessment of immune responses, ten mounted 5T4-specific antibody responses with titers ranging from 10 to > 5,000. IFNgamma ELISPOT responses specific for 5T4 were detected in 11 patients with frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients presented with elevated circulating CEA concentrations, six of whom showed decreases in excess of 50% during chemotherapy and four had CEA levels which remained stable for > 1 month following completion of chemotherapy. Of the 19 intention to treat (ITT) patients, one had a CR, six had PRs and five had SD. Potent 5T4-specific cellular and/or humoral immune responses were induced in all 12 evaluable patients and were detectable in most patients during the period in which chemotherapy was administered. These data demonstrate that TroVax can be layered on top of chemotherapy regimens without any evidence of enhanced toxicity or reduced immunological or therapeutic efficacy.

Harrop R, Drury N, Shingler W, Chikoti P, Redchenko I, Carroll MW, Kingsman SM, Naylor S, Melcher A, Nicholls J et al. 2007. Vaccination of colorectal cancer patients with modified vaccinia ankara encoding the tumor antigen 5T4 (TroVax) given alongside chemotherapy induces potent immune responses. Clin Cancer Res, 13 (15 Pt 1), pp. 4487-4494. | Show Abstract | Read more

PURPOSE: The attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax), has been evaluated in an open-label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during, and after treatment with cycles of 5-fluorouracil, folinic acid, and oxaliplatin. EXPERIMENTAL DESIGN: TroVax was administered to 17 patients with metastatic colorectal cancer. In total, 11 patients were considered to be evaluable for assessment of immunologic responses having received a total of six injections of TroVax, administered before, during, and following completion of chemotherapy. Antibody and cellular responses specific for 5T4 and MVA were monitored throughout the study. RESULTS: Administration of TroVax alongside 5-fluorouracil, folinic acid, and oxaliplatin was safe and well tolerated with no serious adverse events attributed to TroVax. Ten of the 11 evaluable patients mounted 5T4-specific antibody responses with titers ranging from 10 to >1,000. IFNgamma enzyme-linked immunospot responses specific for 5T4 were detected in 10 patients with precursor frequencies exceeding 1 in 1,000 peripheral blood mononuclear cells in 4 patients. Of the 11 evaluable patients, 6 had complete or partial responses. 5T4-specific immune responses, but not MVA-specific immune responses, correlated with clinical benefit. CONCLUSIONS: Potent 5T4-specific cellular and/or antibody responses were induced in all evaluable patients and were still detectable during the period in which chemotherapy was administered. These results suggest that TroVax can be added to chemotherapy regimens without any evidence of enhanced toxicity or reduced immunologic efficacy and may provide additional clinical benefit.

Harrop R, Ryan MG, Myers KA, Redchenko I, Kingsman SM, Carroll MW. 2006. Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4+ T cell dependent and antibody mediated. Cancer Immunol Immunother, 55 (9), pp. 1081-1090. | Show Abstract | Read more

5T4 is a tumor associated antigen that is expressed on the surface of a wide spectrum of human adenocarcinomas. The highly attenuated virus, modified vaccinia Ankara, has been engineered to express human 5T4 (h5T4). In a pre-clinical murine model, the recombinant virus (TroVax) induces protection against challenge with CT26-h5T4 (a syngeneic tumor line expressing h5T4). Anti-tumor activity is long lived, with protection still evident 6 months after the final vaccination. In a therapeutic setting, injection of mice with TroVax results in a reduction in tumor burden of >90%. Depletion of CD8+ T cells has no effect upon therapy in the active treatment model, whereas depletion of CD4+ T cells completely abrogates anti-tumor activity. In a prophylactic setting, depletion of CD4+ and CD8+ T cells after the induction of a h5T4 immune response has no deleterious effect on protection following challenge with CT26-h5T4. In light of these studies, the role of antibodies in protection against tumor challenge was investigated. 5T4 specific polyclonal serum decreased tumor burden by approximately 70%. Thus, we conclude that CD4+ T cells are essential for the induction of a protective immune response and that antibodies are the likely effector moiety in this xenogeneic murine tumor model.

Harrop R, Connolly N, Redchenko I, Valle J, Saunders M, Ryan MG, Myers KA, Drury N, Kingsman SM, Hawkins RE, Carroll MW. 2006. Vaccination of colorectal cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) induces immune responses which correlate with disease control: a phase I/II trial. Clin Cancer Res, 12 (11 Pt 1), pp. 3416-3424. | Show Abstract | Read more

PURPOSE: The highly attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA), encoding the tumor antigen 5T4 (termed TroVax), has been evaluated in an open-label phase I/II study in colorectal cancer patients. The primary objectives were to assess the safety and immunogenicity of ascending doses of TroVax and to determine the biodistribution of the vector. EXPERIMENTAL DESIGN: TroVax was given to 22 patients with metastatic colorectal cancer. Seventeen patients received doses of TroVax ranging from 5 x 10(7) up to 5 x 10(8) plaque-forming units at 0, 4, and 8 weeks and were considered to be evaluable for assessment of immunologic responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector were monitored throughout the study. RESULTS: TroVax was well tolerated in all patients with no serious adverse events attributed to vaccination. Of 17 evaluable patients, 16 showed 5T4-specific cellular responses whereas 14 had detectable antibody levels following vaccination. TroVax was able to boost 5T4-specific immune responses in the presence of MVA neutralizing antibodies. Periods of disease stabilization ranging from 3 to 18 months were observed in five patients, all of whom mounted 5T4-specific immune responses. Furthermore, statistical analysis showed a positive association between the development of a 5T4 (but not MVA) antibody response and patient survival or time to disease progression. CONCLUSION: These data indicate that vaccination with TroVax is safe and well tolerated and that immune responses to 5T4 can be induced without any evidence of autoimmune toxicity. Furthermore, 5T4-specific antibody responses correlate with evidence of disease control.

Redchenko I, Harrop R, Ryan MG, Hawkins RE, Carroll MW. 2006. Identification of a major histocompatibility complex class I-restricted T-cell epitope in the tumour-associated antigen, 5T4. Immunology, 118 (1), pp. 50-57. | Show Abstract | Read more

5T4 is a surface glycoprotein expressed on placental trophoblasts and also on a wide range of human carcinomas. Its highly restricted expression on normal tissues and broad distribution on many carcinomas make 5T4 a promising target for cancer immunotherapy. In the current study, we set out to investigate whether a 5T4-specific cytotoxic T lymphocyte (CTL) repertoire exists in healthy individuals. CD4-depleted peripheral blood mononuclear cells (PBMCs) from blood donors were screened using an ex vivo interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay. A panel of overlapping peptides, spanning the full length of the 5T4 protein, was used as a source of antigen. In the process of screening, one out of 30 blood donors demonstrated a positive ex vivo IFN-gamma ELISPOT response to a single 5T4 peptide. A polyclonal T-cell line was derived from this donor by culturing PBMCs with autologous peptide-pulsed dendritic cells (DCs). The resulting polyclonal T-cell line and clones were tested in a 51Cr-release assay and by ELISPOT and were shown to be peptide specific. Furthermore, antigen-presenting cells (APCs), infected with a viral vector expressing 5T4, were able to stimulate IFN-gamma production by the peptide-specific T-cell clones. A minimal CD8 epitope, PLADLSPFA, has been identified and found to be restricted through human leucocyte antigen (HLA) Cw7. Subsequently, we have demonstrated that HLA-Cw7-positive colorectal cancer patients vaccinated with a recombinant vaccinia viral vector encoding 5T4 (TroVax) are capable of mounting a strong IFN-gamma ELISPOT response to this novel CTL epitope. These findings have potential application in cancer immunotherapy in terms of subunit vaccine design and the monitoring of immune responses induced in patients by 5T4-based therapies.

Cited:

122

Scopus

Harrop R, Connolly N, Redchenko I, Valle J, Saunders M, Ryan MG, Myers KA, Drury N, Kingsman SM, Hawkins RE, Carroll MW. 2006. Vaccination of colorectal cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) induces immune responses which correlate with disease control: A phase I/II trial Clinical Cancer Research, 12 (11 I), pp. 3416-3424. | Show Abstract | Read more

Purpose: The highly attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA), encoding the tumor antigen 5T4 (termed TroVax), has been evaluated in an open-label phase I/II study in colorectal cancer patients. The primary objectives were to assess the safety and immunogenicity of ascending doses of TroVax and to determine the biodistribution of the vector. Experimental Design: TroVax was given to 22 patients with metastatic colorectal cancer. Seventeen patients received doses of TroVax ranging from 5 × 10 7 up to 5 × 10 8 plaque-forming units at 0, 4, and 8 weeks and were considered to be evaluable for assessment of immunologic responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector were monitored throughout the study. Results: TroVax was well tolerated in all patients with no serious adverse events attributed to vaccination. Of 17 evaluable patients, 16 showed 5T4-specific cellular responses whereas 14 had detectable antibody levels following vaccination. TroVax was able to boost 5T4-specific immune responses in the presence of MVA neutralizing antibodies. Periods of disease stabilization ranging from 3 to 18 months were observed in five patients, all of whom mounted 5T4-specific immune responses. Furthermore, statistical analysis showed a positive association between the development of a 5T4 (but not MVA) antibody response and patient survival or time to disease progression. Conclusion: These data indicate that vaccination with TroVax is safe and well tolerated and that immune responses to 5T4 can be induced without any evidence of autoimmune toxicity. Furthermore, 5T4-specific antibody responses correlate with evidence of disease control. © 2006 American Association for Cancer Research.

Shingler WH, Chikoti P, Redchenko I, Harrop R. 2005. Identification and functional validation of MHC Class I epitopes in the tumour-associated antigen 5T4 IMMUNOLOGY, 116 pp. 34-34.

Drury N, Shingler W, Chikoti P, Redchenko I, Kelleher M, Hawkins R, Anthoney A, Steven N, Habib N, Griffiths R et al. 2005. Phase II studies of MVA expressing the tumour antigen 5T4 given with 5-FU based chemotherapies: safety, immunogenicity and clinical responses IMMUNOLOGY, 116 pp. 34-34.

Harrop R, Ryan MG, Golding H, Redchenko I, Carroll MW. 2004. Monitoring of human immunological responses to vaccinia virus. Methods Mol Biol, 269 pp. 243-266. | Show Abstract | Read more

For the last 30 yr, interest in vaccinia virus immune monitoring has focused on the use of the vaccinia virus as a recombinant vaccine vector and the potential detrimental effect of antivector immunity on subsequent vaccination with a recombinant vaccinia virus. However, interest in this area has intensified after the publication of reports suggesting that smallpox may be a major pathogen selected for bioterrorist activities. Owing to the unacceptably high incidence of complications induced by previous effective smallpox vaccine strains, alternative safer strains (e.g., modified vaccinia Ankara [MVA]) are being assessed for their antigenicity in clinical trials. The exact immune effector mechanism responsible for vaccine-induced protection to smallpox infection has not been fully elucidated, although it is believed that neutralizing antibody plays a major role. This chapter describes a simple enzyme-linked immunosorbent assay (ELISA) to quantify vaccinia virus antibody titer. Additionally, to define serum-neutralizing activity, both a classical plaque reduction assay and a high-throughput 96-well plate method based on reduction of recombinant vaccinia virus expressed beta-galactosidase is described. Furthermore, details are given for a T-cell proliferation assay, primarily for monitoring T-helper CD4 activity and an enzyme-linked immunospot (ELISPOT) assay for CD8 analysis. The use of reliable immunological assays is vital in assessing the potential efficacy of new vaccines to protect against smallpox infection.

Leen A, Meij P, Redchenko I, Middeldorp J, Bloemena E, Rickinson A, Blake N. 2001. Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human CD4(+) T-helper 1 responses. J Virol, 75 (18), pp. 8649-8659. | Show Abstract | Read more

Human CD4(+) T-helper 1 cell responses to Epstein-Barr virus (EBV) infection are likely to be important in the maintenance of virus-specific CD8(+) memory and/or as antiviral effectors in their own right. The present work has used overlapping peptides as stimulators of gamma interferon release (i) to identify CD4(+) epitopes within four EBV latent-cycle proteins, i.e., the nuclear antigens EBNA1 and EBNA3C and the latent membrane proteins LMP1 and LMP2, and (ii) to determine the frequency and magnitude of memory responses to these proteins in healthy virus carriers. Responses to EBNA1 and EBNA3C epitopes were detected in the majority of donors, and in the case of EBNA1, their antigen specificity was confirmed by in vitro reactivation and cloning of CD4(+) T cells using protein-loaded dendritic cell stimulators. By contrast, responses to LMP1 and LMP2 epitopes were seen much less frequently. EBV latent-cycle proteins therefore display a marked hierarchy of immunodominance for CD4(+) T-helper 1 cells (EBNA1, EBNA3C > LMP1, LMP2) which is different from that identified for the same proteins with respect to CD8(+)-T-cell responses (EBNA3C > EBNA1 > LMP2 > LMP1). Furthermore, the range of CD4(+) memory T-cell frequencies in peripheral blood of healthy virus carriers was noticeably lower and narrower than the corresponding range of latent antigen-specific CD8(+)-T-cell frequencies.

Redchenko IV, Rickinson AB. 1999. Accessing Epstein-Barr virus-specific T-cell memory with peptide-loaded dendritic cells. J Virol, 73 (1), pp. 334-342. | Show Abstract

The conventional means of studying Epstein-Barr virus (EBV)-induced cytotoxic T-lymphocyte (CTL) memory, by in vitro stimulation with the latently infected autologous lymphoblastoid cell line (LCL), has important limitations. First, it gives no information on memory to lytic cycle antigens; second, it preferentially amplifies the dominant components of latent antigen-specific memory at the expense of key subdominant reactivities. Here we describe an alternative approach, based on in vitro stimulation with epitope peptide-loaded dendritic cells (DCs), which allows one to probe the CTL repertoire for any individual reactivity of choice; this method proved significantly more efficient than stimulation with peptide alone. Using this approach we first show that reactivities to the immunodominant and subdominant lytic cycle epitopes identified by T cells during primary EBV infection are regularly detectable in the CTL memory of virus carriers; this implies that in such carriers chronic virus replication remains under direct T-cell control. We further show that subdominant latent cycle reactivities to epitopes in the latent membrane protein LMP2, though rarely undetectable in LCL-stimulated populations, can be reactivated by DC stimulation and selectively expanded as polyclonal CTL lines; the adoptive transfer of such preparations may be of value in targeting certain EBV-positive malignancies.

Wilson AD, Redchenko I, Williams NA, Morgan AJ. 1998. CD4+ T cells inhibit growth of Epstein-Barr virus-transformed B cells through CD95-CD95 ligand-mediated apoptosis. Int Immunol, 10 (8), pp. 1149-1157. | Show Abstract | Read more

Greater than 90% of the human population acquire Epstein-Barr virus (EBV) in infancy and retain a lifelong latent infection without any clinical consequences. Nevertheless EBV has been identified as the causal agent of infectious mononucleosis, and is associated with several tumours including endemic Burkitt's lymphoma and B cell lymphomas in immunosupressed patients. B cells infected with EBV are transformed in vitro and grow continuously as lymphoblastoid cell lines. The growth of EBV-transformed B cells in vivo is controlled by the immune system. Studies on immunity to EBV have mainly focused on MHC class I-restricted CD8+ cytotoxic T cells specific for viral latent antigens. Here it is reported that in vitro stimulation of peripheral blood lymphocytes by autologous EBV-infected B cells, which have been induced to express lytic cycle antigens, gives rise to a predominantly CD4+ T cell response. Furthermore, the growth of EBV-infected B cells can also be regulated by these activated CD4+ T cells through apoptosis mediated by CD95-CD95 ligand (CD95L). CD95-CD95L-mediated apoptosis is an important mechanism of normal B cell growth regulation. As EBV-transformed B cells remain susceptible to this mechanism, the control of EBV in vivo may be not only by virus-specific CD8+ cytotoxic T cell immunity but also by normal mechanisms of immune regulation of B cell growth.

Blake N, Lee S, Redchenko I, Thomas W, Steven N, Leese A, Steigerwald-Mullen P, Kurilla MG, Frappier L, Rickinson A. 1997. Human CD8+ T cell responses to EBV EBNA1: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing. Immunity, 7 (6), pp. 791-802. | Show Abstract | Read more

Epstein-Barr virus (EBV)-induced cytotoxic T lymphocyte (CTL) responses have been detected against many EBV antigens but not the nuclear antigen EBNA1; this has been attributed to the presence of a glycine-alanine repeat (GAr) domain in the protein. Here we describe the isolation of human CD8+ CTL clones recognizing EBNA1-specific peptides in the context of HLA-B35.01 and HLA-A2.03. Using these clones, we show that full-length EBNA1 is not presented when expressed endogenously in target cells, whereas the GAr-deleted form is presented efficiently. However, when supplied as an exogenous antigen, the full-length protein can be presented on HLA class I molecules by a TAP-independent pathway; this may explain how EBNA1-specific CTLs are primed in vivo.

Saschenko LP, Gnuchev NV, Redchenko IV, Kabanova OD, Lukjianova TI, Blishchenko LYu, Satpaev DK, Chertov OYu. 1994. Contribution of membrane-associated cytotoxic proteins to cytolysis of L929 and K562 target cells mediated by LAK cells with different phenotypes. Immunol Lett, 39 (3), pp. 243-247. | Show Abstract | Read more

We have demonstrated that the relative contribution of secreted and membrane-associated proteins to the cytotoxicity of LAK cells depended on LAK cell phenotype: the cytotoxicity of CD16+ CD8+ CD3- LAK cells was associated mainly with membrane-bound proteins, and the activity of CD3+ CD8+ CD16- LAK cells was due mainly to secreted soluble proteins. The cytotoxic activity of membrane fractions of LAK cells against cell line L929 was determined by 40-, 32- and 21-kDa proteins for LAK cells bearing NK-specific markers and due to proteins of 34 and 21 kDa in the case of 'CTL-like' LAK-cells.

Chertov OYu, Ermolaeva MV, Satpaev DK, Saschenko LP, Kabanova OD, Lukanidin EM, Lukjianova TI, Redchenko IV, Blishchenko LYu, Gnuchev NV. 1994. Inhibitory effect of calf fetuin on the cytotoxic activity of LAK cell-derived factors and tumor necrosis factor. Immunol Lett, 42 (1-2), pp. 97-100. | Show Abstract | Read more

A protein-inhibiting LAK cell-mediated cytotoxicity was isolated from a LAK cell-conditioned medium. The N-terminal amino acid sequence of this protein appeared to be identical to fetal calf fetuin. Pure isolated fetuin, as well as commercially available preparations of this protein, were shown to inhibit cytotoxic activity of both cytotoxic proteins released by LAK cells and TNF.

Sashchenko LP, Gnuchev NV, Lukjanova TI, Redchenko IV, Kabanova OD, Lukanidin EM, Blishchenko EYu, Satpaev DK, Khaidukov SV, Chertov OYu. 1993. Time-dependent changes of LAK cell phenotypes correlate with the secretion of different cytotoxic proteins. Immunol Lett, 37 (2-3), pp. 153-157. | Show Abstract | Read more

Human lymphokine-activated killer (LAK) cells were generated from peripheral blood lymphocytes (PBL) of normal volunteers by interleukin-2 (IL-2) stimulation for 1-8 days. During the first 3 days the surface marker CD16 characteristic for natural killer (NK) cells was expressed and later the CD3 marker characteristic for cytotoxic T cells became predominant. The conditioned media of LAK cells collected after interaction of LAK cells with K562 target cells was chromatographically separated into two cytotoxic fractions: F1 and F2. It was demonstrated that fraction F1 contained cytotoxic proteins having molecular weights of 30 and 40 kDa, and fraction F2 contained cytotoxic proteins having molecular weights of 22, 38 and 75 kDa. The presence of the proteins in each of these two fractions correlated with the phenotype changes of LAK cells: the F2 cytotoxic proteins were characteristic for NK-like cells, and the F1 proteins for cytotoxic T-lymphocyte (CTL)-like phenotypes.

Sashchenko LP, Gnuchev NV, Kabanova OD, Blishchenko EI, Luk'ianova TI, Redchenko IV, Savtsova ZD, Chertov OI, Lukanidin EM. 1992. [Functional changes in lymphokine-activated lymphocytes depending on the incubation time with interleukin-2]. Dokl Akad Nauk, 324 (2), pp. 475-479.

Sashchenko LP, Gnuchev NV, Lukyanova TI, Kabanova OD, Redchenko IV, Blishchenko Yu E, Satpaev DK, Khaidukov SV, Chertov Yu O, Lukanidin EM. 1992. Effect of interleukin-2 on the cytolytic activity, expression of surface markers and secretion of cytotoxic proteins by lymphokin-activated killer cells Eksperimentalnaya Onkologiya, 14 (5), pp. 55-60.

2414