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M A Cheever

Publications and source records attributed to M A Cheever.

At least 19 recordsLinked to original sources
PubMed1997

Identification of rat prostatic steroid-binding protein as a target antigen of experimental autoimmune prostatitis: implications for prostate cancer therapy.

The long term goal of this study is to develop autoimmune prostatitis as a therapy for prostate cancer. An immune attack capable of destroying normal prostate epithelial cells should also destroy malignant prostate tissue and provide therapeutic benefit in cancer patients. The current study was initiated to identify antigenic targets for experimental autoimmune prostatitis on the assumption that such proteins might also be suitable targets for immunotherapy of prostate cancer. Male Lewis rats were immunized with syngeneic prostate homogenates, and the immune sera were used to screen prostate proteins for immunoreactivity by Western blot analysis. The dominant protein recognized by the immune sera was purified by ion exchange chromatography and reverse phase HPLC. Microsequence analysis of two polypeptide components of this immunodominant protein demonstrated N-terminal sequences identical with two of the three component chains of rat prostatic steroid-binding protein (PSBP). T cell responses to PSBP were also detected in rats immunized with prostate homogenate. Immunizing male rats with purified PSBP induced vigorous Ab and T cell responses. Significant prostate inflammation was observed in some rats immunized with PSBP. Adoptive transfer of T cells immune to PSBP induced rapid and severe destructive autoimmune prostatitis. These results demonstrate that PSBP is a major target Ag of experimental autoimmune prostatitis in a rat model and may serve as a target Ag for vaccine and T cell therapy against prostate cancer.

Animals↗
PubMed1997

HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer.

The HER-2/neu oncogenic protein is a tumor antigen. Some patients with cancer have a preexistent immune response directed against the HER-2/neu protein. Effective cancer vaccines targeting HER-2/neu will be able to boost this immunity to potentially therapeutic levels. In addition, HER-2/neu-directed monoclonal antibody therapy has been effective in eradicating malignancy in animal models and has shown benefit in the treatment of human HER-2/neu-overexpressing cancers. This review outlines studies that define HER-2/neu-specific immunity in patients with cancer and overviews the current vaccine strategies for generating or augmenting neu-specific immunity. The potential problems associated with eliciting HER-2/neu-specific immunity are addressed, including the question of precipitating autoimmune toxicity against this "self" -protein and the mechanisms of immunological escape that may play a role in preventing effective function of the HER-2/neu-specific immune response. Finally, antibody-based HER-2/neu-directed therapies are overviewed. HER-2/neu is a prototype antigen for groups investigating innovative modifications of monoclonal antibody technology, and cutting edge therapies targeting this antigen are being contemplated for clinical use in the treatment of human malignancy. Immune-based treatments designed to target the HER-2/neu oncogenic protein will soon give the clinical oncologist new therapeutic weapons, directed against a biologically relevant tumor-related protein, with which to fight cancer.

Adjuvants, Immunologic↗
PubMed1997

Identification of Her-2/Neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD.8.

The Her-2/neu protooncogene is associated with malignant transformation and aggressive disease. Because of its overexpression in tumor cells and because it has been shown to be immunogenic, this protein represents an excellent target for T-cell immunotherapy. By identifying potential HLA-A2.1-binding peptides from the Her-2/neu sequence, peptides were selected as candidate T-cell epitopes. The immunogenicity of each peptide was evaluated by priming double transgenic mice expressing both the human (hu) CD8 and HLA-A2.1 molecules with synthetic peptides corresponding to these sequences. Because of the lack of interaction between murine CD8 and HLA-A2.1, expression of huCD8 on murine cells facilitates recognition of HLA molecules on human tumor cell lines. This led to the identification of two peptides that elicit an A2-restricted CTL response, one of which has not been previously identified. Both peptide-specific CTL populations were able to specifically lyse A2.1 and Her-2/neu expressing human tumor cells originating from a variety of tissues, demonstrating the utility of this murine model in identifying peptides presented by human cells. However, several Her-2/neu peptides previously reported to be immunogenic for human CTL were found not to be immunogenic in transgenic mice. The basis for these discrepancies is discussed.

Amino Acid Sequence↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines.

The current studies evaluate granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant. An important issue for developing vaccine therapy for human malignancy is identifying adjuvants that can elicit T-cell responses to proteins and peptides derived from "self" tumor antigens. GM-CSF, in vitro, stimulates the growth of antigen-presenting cells such as dendritic cells and macrophages. Initial experiments examined whether GM-CSF injected into the skin of rats could affect the number or character of antigen presenting cells, measured as class II major histocompatability complex expressing cells, in lymph nodes draining the injection site. Intradermal (id) inoculation of GM-CSF every 24 hours for a total of five inoculations resulted in an increase of class II+ fluorescing cells that peaked at the fourth inoculation. Subcutaneous (sq) inoculation resulted in an increase of class II+ fluorescing cells that peaked following the second inoculation, then decreased over time. Using this schema for "conditioning" the inoculation site, GM-CSF was administered id or sq for five injections and a foreign antigen, tetanus toxoid (tt), was given at the beginning or the end of the immunization cycle. Id immunization was more effective than sq at eliciting tt specific immunity. In addition, GM-CSF id, administered as a single dose with antigen, compared favorably with complete Freund's adjuvant (CFA) and alum in eliciting tt specific antibody and cellular immunity. We have shown that immunity to rat neu (c-erbB-2) protein, an oncogenic self protein, can be generated in rats by immunization with peptides derived from the normal rat neu sequence plus CFA. The current study demonstrates that rat neu peptides inoculated with GM-CSF could elicit a strong delayed type hypersensitivity reaction (DTH) response, whereas peptides alone were non-immunogenic. GM-CSF was as effective as CFA in generating rat neu specific DTH responses after immunization with a neu peptide based vaccine. Soluble GM-CSF is a potent adjuvant for the generation of immune responses to foreign proteins as well as peptides derived from a self tumor antigen.

Adjuvants, Immunologic↗
PubMed1996

Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, oncogenic self-protein.

HER-2/neu, an overexpressed oncogenic protein, has been proposed as a human cancer vaccine target. HER-2/neu is a "self" protein, however, and methods of vaccine strategies that would be effective in immunizing patients to a "self" tumor Ag have not been established. Many of the tumor Ags defined in humans are nonmutated self proteins, e.g., MAGE, and overcoming tolerance may be key in the generation of effective anti-tumor immunity. One theory states that tolerance to self proteins is directed only to dominant epitopes of proteins and not to every portion of the protein. Accordingly, tolerance can be circumvented by immunization to peptide fragments, but not whole protein. The studies outlined here demonstrate rat neu-specific immunity could be elicited in rats by vaccination with immunogenic rat neu peptides, but not by immunization with the intact protein. A rat model was used since rat neu protein is 89% homologous to human HER-2/neu protein and has a similar tissue distribution and level of expression. Rats were immunized with groups of peptides derived from the amino acid sequence of the intracellular domain or extracellular domain of rat neu protein and both groups developed CD4+ T cell immunity and Ab immunity to rat neu peptides and protein. Animals immunized in a similar fashion with intact purified rat neu protein did not develop Ab or T cell immunity to rat neu. Furthermore, rats that developed neu-specific immunity showed no histopathologic evidence of autoimmunity directed against organs expressing basal levels of rat neu protein. These studies suggest an immunization strategy that might be effective in human cancer vaccines targeting self tumor Ag.

Amino Acid Sequence↗
PubMed1996

Oncogenic proteins as tumor antigens.

Human immune responses to oncogenic proteins have been reported and are continuing to be defined. Immunity to nonmutated overexpressed oncoproteins as well as to mutated or unique cancer-specific oncoproteins has been identified. Immune system based treatments targeting oncogenic proteins have shown therapeutic efficacy in animals models and are currently being translated into human clinical trials.

Animals↗
PubMed1996

Identification of a gag-encoded cytotoxic T-lymphocyte epitope from FBL-3 leukemia shared by Friend, Moloney, and Rauscher murine leukemia virus-induced tumors.

FBL-3 is a highly immunogenic murine leukemia of C57BL/6 origin induced by Friend murine leukemia virus (MuLV). Immunization of C57BL/6 mice with FBL-3 readily elicits CD8+ cytotoxic T lymphocytes (CTL) capable of lysing FBL-3 as well as syngeneic leukemias induced by Moloney and Rauscher MuLV. The aim of this current study was to identify the immunogenic epitope(s) recognized by the FBL-3-specific CD8+ CTL. A series of FBL-3-specific CD8+ CTL clones were generated from C57BL/6 mice immunized to FBL-3. The majority of CTL clones (32 of 38) were specific for F-MuLV gag-encoded antigen. By using a series of recombinant vaccinia viruses expressing full-length and truncated F-MuLV gag genes, the antigenic epitope recognized by the FBL-3 gag-specific CTL clones, as well as by bulk-cultured CTL from spleens of mice immune to FBL-3, was localized to the leader sequence of gPr80gag protein. The precise amino acid sequence of the CTL epitope in the leader sequence was identified as CCLCLTVFL (positions 85-93) by examining lysis of targets incubated with a series of synthetic leader sequence peptides. No evidence of other CTL epitopes in the gPr80gag or Pr65gag core virion structural polyproteins was found. The identity of CCLCLTVFL as the target peptide was validated by showing that immunization with the peptide elicited CTL that lysed FBL-3. The CTL elicited by the Gag peptide also specifically lysed syngeneic leukemia cells induced by Moloney and Rauscher MuLV (MBL-2 and RBL-5). The transmembrane peptide was shown to be the major gag-encoded antigenic epitope recognized by bulk-cultured CTL derived from C57BL/6 mice immunized to MBL-2 or RBL-5. Thus, the CTL epitope of FBL-3 is localized to the transmembrane anchor domain of the nonstructural Gag polyprotein and is shared by leukemia/lymphoma cell lines induced by Friend, Moloney, and Rauscher MuLV.

Animals↗
PubMed1996

[Probability of vaccine therapy for pancreas cancer].

To explore the possibility of vaccine therapy for pancreatic cancer using ras oncogenic protein related antigen we studied whether cytotoxic T lymphocyte for tumor rejection can be induced by vaccination using the peptide relating mutated ras protein. Splenocytes from mice immunized by peptide (9-15 mer) relating mutated ras protein with normal splenocytes specifically increased in the culture with the peptide. The harvested splenic lymphocytes from the mice had peptide specific lysis against B 6 fibroblast incubated with the peptide. These results suggested that immunization using the peptide relating mutated ras peptide with autologous antigen presenting cell can be a vaccine therapy for pancreatic cancer.

Animals↗
PubMed1995

CD4+ T-cell immunity to mutated ras protein in pancreatic and colon cancer patients.

Mutated p21 ras proteins contain single substituted amino acid residues and represent cancer-specific proteins. The current study examined whether primed T cell immunity to mutant p21 ras proteins and/or peptides can be detected in patients with pancreatic or colon cancer. Studies focused on the aspartic acid substitution in amino acid position 12 (denoted D12) as the commonest mutation in gastrointestinal malignancy. Peripheral blood lymphocytes from patients or normal individuals were tested for the ability to proliferate in response to normal or mutated ras peptides or proteins. T-cell responses were defined as a stimulation index of > 2.0. Results showed that 7 of 16 (44%) pancreatic cancer patients responded to ras-D12 peptide. Responses to ras-D12 protein were studied in only the last four patients that responded to D12 peptides. Three of the 4 patients that responded to ras-D12 peptide showed a substantial response to p21 ras-D12 protein (stimulation indices of 12, 8, and 24). Specificity was validated by examining responses to normal and alternate ras peptides and proteins. T-cell responses to ras-D12 peptides were detected in only 2 of 25 (8%) colon cancer patients. None of 11 normal individuals tested had positive responses to normal or mutant ras p21 proteins and/or peptides. Thus, CD4+ T-cell immunity to the mutated segment of ras protein is present in some patients with gastrointestinal cancer.

Amino Acid Sequence↗
PubMed1995

Generation of immunostimulatory dendritic cells from human CD34+ hematopoietic progenitor cells of the bone marrow and peripheral blood.

Dendritic antigen-presenting cells are considered to be the most effective stimulators of T cell immunity. The use of dendritic cells has been proposed to generate therapeutic T cell responses to tumor antigens in cancer patients. One limitation is that the number of dendritic cells in peripheral blood is exceedingly low. Dendritic cells originate from CD34+ hematopoietic progenitor cells (HPC) which are present in the bone marrow and in small numbers in peripheral blood. CD34+ HPC can be mobilized into the peripheral blood by in vivo administration of granulocyte-colony-stimulating factor. The aim of the current study was to determine whether functional dendritic cells could be elicited and grown in vitro from CD34+ HPC derived from bone marrow or granulocyte-colony-stimulating factor-mobilized peripheral blood. Culture of CD34+ HPC with granulocyte-macrophage-colony-stimulating factor and tumor necrosis factor alpha yielded a heterogeneous cell population containing cells with typical dendritic morphology. Phenotypic studies demonstrated a loss of the CD34 molecule over 1 week and an increase in cells expressing surface markers associated with dendritic cells, CD1a, CD80 (B7/BB1), CD4, CD14, HLA-DR, and CD64 (Fc gamma RI). Function was validated in experiments showing that cultured cells could stimulate proliferation of allogeneic CD4+ and CD8+ T lymphocytes. Antigen-presenting capacity was further confirmed in experiments showing that cultured cells could effectively stimulate tetanus toxoid-specific responses and HER-2/neu peptide-specific responses. The derivation and expansion of dendritic cells from cultured bone marrow or granulocyte-colony-stimulating factor-mobilized CD34+ HPC may provide adequate numbers for testing of dendritic cells in clinical studies, such as vaccine and T cell therapy trials.

Antigen Presentation↗
PubMed1995

Serum immunoglobulins specific for intracellular proteins of squamous cell carcinoma.

OBJECTIVE: To determine an autologous humoral immune response to squamous cell carcinoma (SCC) intracellular proteins in patients with SCC. DESIGN: Intracellular proteins were isolated from 25 different cultured SCC lines. The proteins were used as a source of antigens to measure IgA, IgE, and IgG responses in the serum samples of patients and controls. Antibody response was assessed in both unfractionated and fractionated intracellular proteins. PATIENTS: The serum samples of 65 patients with SCC and of 65 age- and gender-matched controls were tested. RESULTS: Antibodies to SCC intracellular proteins were detected in the serum samples of 40 (62%) of the 65 patients with SCC and in the serum samples of 46 (71%) of 65 controls. Thirty (46%) of the patients with SCC and 40 (62%) of the controls had IgE responses, 18 (28%) of the patients and one (2%) of the controls had IgA responses, and 17 (26%) of the patients and 14 (22%) of the controls had IgG responses. An inverse relation was noted between detectable IgE responses and IgA or IgG responses in the patients and the controls. The analysis of antibody response indicated that 28 molecules were recognized predominantly by the serum samples of patients with SCC, but not by the serum samples of controls. CONCLUSIONS: A substantial proportion of patients with SCC and of controls exhibited an autologous humoral immune response to SCC intracellular proteins. The IgE responses to SCC intracellular proteins were inversely related to IgA or to IgG responses. Different antibody isotypes normally cause markedly different immune functions, and may suggest different roles for the existent immune responses to SCC antigens. We identified many tumor-associated antigens that were selectively recognized by the serum samples of patients with SCC. These antigens could be used to define molecular studies of immune surveillance and selection, and may represent appropriate targets for immunotherapy.

Autoradiography↗
PubMed1994

Retroviral transduction of protein kinase C-gamma into tumor-specific T cells allows antigen-independent long-term growth in IL-2 with retention of functional specificity in vitro and ability to mediate tumor therapy in vivo.

The aim of our study was to examine the potential usefulness of transducing the protein kinase C-gamma (PKC-gamma) cDNA gene into tumor-specific T cells as a technique for facilitating the generation of large numbers of functional Ag-specific T for tumor therapy. Murine CD8+, F-MuLV gag-specific CTL clones, and CD4+, F-MuLV env-specific Th clones, as well as bulk-cultured T cell lines with defined Ag specificity to FBL-3, a Friend murine leukemia virus (F-MuLV)-induced tumor, were transduced with a retroviral vector pZipNeoPKC-gamma and selected in G418. The results demonstrated that PKC-gamma-transduced clones remained activated in culture, as evidenced by continued expression of up-regulated levels of IL-2R, which were as high after 6 mo in culture without Ag restimulation as 24 h after Ag stimulation. In vitro functional studies demonstrated that PKC-gamma-transduced CD8+ T cell clones maintained specific cytolytic activity to FBL-3, and PKC-gamma-transduced CD4+ T cell clones maintained specific proliferative activity to FBL-3 or F-MuLV Ag presented by irradiated syngeneic APC. Short-term bulk-cultured T cells specific to FBL-3 were also transduced and could be grown long term in vitro with maintenance of functional specificity. In vivo study showed that PKC-gamma-transduced CD4+ T cells were able to proliferate in response to Ag plus IL-2 stimulation in vivo in a similar pattern as the parental T cells. Therapy with adoptively transferred PKC-gamma-transduced T cell clones and lines into syngeneic mice, with or without FBL-3 tumor, showed that the PKC-gamma-transduced T cells were not tumorigenic and were effective in curing mice with disseminated FBL-3.

Animals↗
PubMed1994

Donor T cells can be induced to grow and survive long term in vivo without previous host immunosuppression.

To examine whether donor T cells can grow and survive long term in hosts without previous immunosuppression, cultured T cells (B6/Thy 1.1) specific to FBL-3 tumor were adoptively transferred into normal B6/Thy 1.2 mice and induced to proliferate in vivo by specific stimulation with irradiated FBL-3. Donor T cells residing in the spleen and ascites of hosts were identified and quantified by use of Ab to the Thy-1 allele. The results demonstrated that on day 7 after transfer, donor T cells in greater numbers than input (1.2-fold) could be recovered. By day 35, donor T cells had decreased to approximately 10% of T cells input. Administration of IL-2 at doses of 2,500 or 25,000 U/day for 7 days preferentially increased the growth of Ag-activated donor T cells rather than host lymphocytes, and increased both the short term growth on day 7 (6.6-fold and 14.5-fold greater than input, respectively) and the long term survival on day 35 (0.75-fold and 3.15-fold of input, respectively) of donor T cells. The combination of CY pretreatment plus low dose IL-2 (2,500 U/day) increased donor T cell growth over and above that of either manipulation alone. However, with higher dose IL-2 to 25,000 U/day, donor T cell growth was equivalent in CY-pretreated and normal hosts (18-fold vs 16-fold increase, respectively; p > 0.05). With either dose of IL-2 there was no significant difference in the survival of donor T cells on day 35 in CY-pretreated vs normal hosts. Functional assay confirmed that specific cytolytic function of donor T cells could be maintained in hosts without previous immunosuppression. Accordingly, established disseminated FBL-3 leukemia could be cured without CY treatment, in a regimen using 10(7) cultured immune T cells plus IL-2 (25,000 U/day x 7 days). Thus, adoptively transferred donor T cells can be grown to large numbers and survive long term in vivo with maintenance of substantial function without the necessity of previous host immunosuppression.

Animals↗
PubMed1994

In vitro generation of human cytolytic T-cells specific for peptides derived from the HER-2/neu protooncogene protein.

The development of T-cell therapy for the treatment of human malignancy has been hindered, in large part, by a lack of identifiable tumor antigens. Studies to identify potential T-cell targets in humans have been difficult because of practical problems limiting the use of in vivo immunization and a lack of reproducible in vitro priming methods. Oncogenic proteins are involved in malignant transformation and maintenance of the transformed phenotype and theoretically are potential targets to T-cell therapy. HER-2/neu protein is a protooncogene product overexpressed in a variety of human malignancies and is associated with malignant transformation and aggressive disease in human breast cancer. Previous studies have shown that some patients with breast cancer have existent helper/inducer T-cell immunity to p185HER-2/neu protein and peptides. The current study represents initial attempts to identify candidate cytotoxic T-lymphocyte (CTL) epitopes. Synthetic peptides were constructed identical to HER-2/neu protein segments with amino acid motifs similar to the published motif for HLA-2.1-binding peptides. Four peptides were synthesized and two were shown to be avid binders to HLA-A2.1. Two of the four peptides could be shown to elicit peptide-specific CTL by primary in vitro immunization in a culture system using peripheral blood lymphocytes from a normal individual homozygous for HLA-A2. p185HER-2/neu protooncogene protein contains immunogenic epitopes capable of generating human CD8+ CTL. The identification of candidate CTL epitopes will allow studies to determine whether some cancer patients have existent CTL immunity to HER-2/neu protein. The demonstrated ability to generate human peptide-specific CTL in vitro allows screening of other oncogenic proteins to identify candidate T-cell epitopes potentially useful for future immunotherapy studies.

Amino Acid Sequence↗
PubMed1994

T-cells for tumor therapy can be obtained from antigen-loaded sponge implants.

The aim of the current study was to evaluate the therapeutic use of tumor-specific T-cells obtained from s.c. Ag (antigen)-loaded sponge implants. Naive C57BL/6 mice were implanted with small, polyurethane sponges containing irradiated FBL-3 tumor cells. On day 10, cells that had accumulated in the sponges were harvested and tested for specific cytolytic and proliferative function in vitro. The results demonstrated that CD8+ and CD4+ T-cells immune to FBL-3 could both be primed in and obtained from the Ag-loaded sponge implants. Limiting dilution analysis demonstrated that the frequency of FBL-3-specific cytotoxic T-lymphocytes elicited from Ag-loaded sponges was four times greater than the frequency from draining lymph nodes and at least 50 times greater than from spleen and peripheral blood. Tumor-specific T-cells could similarly be obtained from Ag-loaded sponges implanted into previously primed mice and into mice bearing disseminated FBL-3. In both circumstances, elicited T-cells exhibited much higher cytolytic activity than T-cells from sponges implanted in naive mice, indicating an in situ accumulation and expansion of primed T-cells in response to the antigen stimulation. Tumor-specific T-cells obtained from Ag-loaded sponge implants could be grown long-term in vitro by periodic restimulation with irradiated FBL-3 and low concentrations of interleukin 2. Adoptive transfer of the resultant expanded T-cell lines into mice with disseminated FBL-3 revealed that cultured sponge-infiltrating T-cells could mediate effective antitumor therapy. Thus, in vivo immunization with Ag-loaded sponges provides a potentially useful technique for procuring primed, Ag-specific T-cells for tumor therapy.

Animals↗
PubMed1994

Lysis of ras oncogene-transformed cells by specific cytotoxic T lymphocytes elicited by primary in vitro immunization with mutated ras peptide.

Ras protooncogenes are activated by characteristic point mutations in a wide variety of malignancies. The expressed p21ras proteins are oncogenic by virtue of single substituted amino acids, usually at position 12 or 61 of the 189-residue p21ras protein. In the current study, the ability of class I major histocompatibility complex (MHC)-restricted T cells to recognize the altered segment of a transforming p21ras protein and to lyse cells transformed by the corresponding ras oncogene was examined. Synthetic ras peptides encompassing the common activating substitution of leucine for glutamine at position 61 were constructed with an amino acid motif appropriate for binding to the H-2Kb murine class I MHC molecule. Cytotoxic T lymphocytes (CTL) specific for bound ras leucine 61 peptide were elicited by in vitro immunization of normal lymphocytes with synthetic peptides. The ras peptide-induced CTL specifically lysed syngeneic fibroblasts transformed by an activated ras gene encoding oncogenic p21ras protein containing the same single amino acid substitution. Thus, in some circumstances, mutated p21ras protein can serve as a tumor-specific antigen.

Amino Acid Sequence↗
PubMed1994

Immunity to the HER-2/neu oncogenic protein.

The study of oncogenic viruses led to the discovery that transforming retroviruses contain oncogenes homologous with and/or derived from cellular proto-oncogenes. In humans malignant transformation is often the result of the activation of proto-oncogenes. Normal proto-oncogenes can be activated to transforming proto-oncogenes by a variety of mechanisms including point mutation, translocation and amplification. Development of successful strategies for the immunotherapy of human cancers is an area of intense investigation. Part of the problem in developing cancer-specific immunotherapy has been the lack of well-defined tumour antigens. Our laboratory has focused on the question of whether oncogenic proteins expressed by transforming proto-oncogenes can serve as targets for immune attack. Some patients with HER-2/Neu-positive breast cancer have an existent immune response to the HER-2/neu protein with no clinical signs of autoimmunity, supporting the idea that overexpressed oncogenic proteins can be targeted in therapy without fear of destructive autoimmunity. The identification of candidate cytotoxic T lymphocyte epitopes might allow the generation of tumour-specific cytotoxic T lymphocytes for use in therapy and identify potential epitopes for peptide vaccines.

Amino Acid Sequence↗