Antigens for cancer immunotherapy

Neller, Michelle A.; López, José Alejandro; Schmidt, Chris

doi:10.1016/j.smim.2008.09.006

Cited by 151 publications

(118 citation statements)

References 173 publications

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“…Common tumor antigen-based immunotherapies can potentially selectively target cancer cells; however, this form of immunotherapy has yet to yield consistent meaningful clinical outcomes (2). It has been hypothesized that patientspecific neoepitopes, derived from protein-altering mutational events, result in stronger immune responses against the expressing tumor cells than common tumor antigens (3).…”

Section: Introductionmentioning

confidence: 99%

Exome Sequencing to Predict Neoantigens in Melanoma

Pritchard

Burel

Neller

et al. 2015

Cancer Immunology Research

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The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to use for mutated peptide screening. Five patients were investigated, three of whom had a durable complete response (CR; 15þ years) in an autologous melanoma-pulsed dendritic cell clinical trial. We identified seven mutated antigens in total that stimulated T-effector memory cells in two of the five patients. While the procedure did not result in clinically applicable neoantigens for all patients, those identified were likely important in tumor clearance, leading to durable CR. The nature of the screening process allows results to be obtained rapidly and is easily applicable to a wide variety of different tumor types.

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Section: Introductionmentioning

confidence: 99%

Exome Sequencing to Predict Neoantigens in Melanoma

Pritchard

Burel

Neller

et al. 2015

Cancer Immunology Research

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“…Tumor vaccines fill an emerging niche in comprehensive cancer care. There is recent clinical evidence to suggest that inducing polyclonal anti-tumor T cell responses against TAAs in heterogeneous tumor populations can efficiently inhibit disseminated tumor progression (37). The use of PLGA MPs offers many unique features for antigen delivery, as MPs can be used to co-encapsulate adjuvant or target cellular subsets via surface modifications (11,38).…”

Section: Discussionmentioning

confidence: 99%

A Therapeutic Microparticle-Based Tumor Lysate Vaccine Reduces Spontaneous Metastases in Murine Breast Cancer

Gross

Wongrakpanich

Francis

et al. 2014

AAPS J

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Abstract. Metastatic breast cancer is currently incurable, and available therapies are associated with severe toxicities. Induction of protective anti-tumor immunity is a promising therapeutic approach for disseminated breast cancer, as immune responses are (i) systemic; (ii) antigen-specific; and (iii) capable of generating long-lived "memory" populations that protect against future tumor recurrences. Pursuant with this approach, we have developed a novel heterologous prime/boost vaccination regimen that reduces spontaneous lung metastases in mice with established murine 4T1 adenocarcinoma breast tumors. In our studies, mice were orthotopically challenged with luciferase-expressing 4T1 tumor cells; luciferase expression was retained in vivo, enabling us to quantitatively track metastatic tumor growth via bioluminescent imaging. On day 6 post-challenge, mice received a therapeutic "prime" consisting of bulk tumor lysates encapsulated in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs). On day 11, mice received a "boost" composed of free tumor lysates plus a cocktail of Toll-like receptor (TLR)-stimulating adjuvants. Tumor progression was monitored in vaccinated and untreated mice for 25 days, a time at which 100% of untreated mice had detectable lung tumors. PLGA MPs injected subcutaneously trafficked to draining lymph nodes and were efficiently phagocytosed by dendritic cells (DCs) within 48 h. Our combination therapy reduced metastatic lung tumor burdens by 42% and did not induce autoimmunity. These findings illustrate that vaccines based upon MP delivery of tumor lysates can form the basis of an effective treatment for metastatic breast cancer and suggest that similar approaches may be both efficacious and well-tolerated in the clinic.

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“…The gene manifests expression in activated lymphocytes T CD4 + and T CD8 + . It negatively regulates (inhibits) proliferation of lymphocytes T, inhibiting inflow of Ca 2+ ions to the cell, induced by TCR receptor, following binding of an antigenic determinant and controlling number of T memory lymphocytes [48,49].…”

Section: Description Of Principles In Tumour Treatment Taking Into Amentioning

confidence: 99%

Problems of Cancer Treatment. Part 2. Treatment Based on Modification of Anticancer Immunological Responses in Therapy

Kawiak

Hoser

Domagała‐Kulawik

2017

Advances in Cell Biology

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Summary:Here we present the concept of making own patient's anti-cancer treatment more efficient and starting at testing the efficacy of immunological system. The respective tests are suggested, with special attention devoted to tumour-induced microenvironmental changes. The tumour should be considered to represent a complex tissue in which the cancer cells communicate directly and indirectly with the surrounding cellular immunological surrounding and develope traits that promote their own survival. The results of tests allow to propose a rational, individually profiled treatment of a patient, especially directed to elimination of blocks inhibiting the immunological system due to effects of cancer cells. The elimination can be implemented using commercially available antibodies, targeted at the cell surface receptors for inhibitors of T lymphocytes (CTLA-4 and PD-1). Outcome of the therapy is slow to appear and the results used to be selective. Some patients gain long term improvement and respective predictive markers are now tested. It is assumed that the future anti-cancer therapy will be individually targeted, based on individual tests and an assistance of own immunological system of the cancer patient.

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Antigens for cancer immunotherapy

Cited by 151 publications

References 173 publications

Exome Sequencing to Predict Neoantigens in Melanoma

Exome Sequencing to Predict Neoantigens in Melanoma

A Therapeutic Microparticle-Based Tumor Lysate Vaccine Reduces Spontaneous Metastases in Murine Breast Cancer

Problems of Cancer Treatment. Part 2. Treatment Based on Modification of Anticancer Immunological Responses in Therapy

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