Immunomodulatory properties of antineoplastic drugs administered in conjunction with GM-CSF-secreting cancer cell vaccines.

Nigam, Ankesh; Yacavone, Robert F.; Zahurak, Marianna; Johns, Christina M.S.; Pardoll, Drew M.; Piantadosi, Steven; Nelson, William G.

doi:10.3892/ijo.12.1.161

Cited by 30 publications

(31 citation statements)

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“…In tolerant neu transgenic mice, giving Doxorubicin one week after vaccination augments vaccine activity (45). Similarly, Doxorubicin given one week after vaccination in the CT26 model of colon cancer augmented antitumor immunity, resulting in a higher CD8 + T cell response (57). These effects may be due to modulation of tumor cells themselves as discussed previously, with caspase and calreticulin induction rendering them more immunogenic.…”

Section: Chemotherapy and The Host Immunologic Milieumentioning

confidence: 93%

Chemotherapy and tumor immunity: an unexpected collaboration

Emens

2008

Front Biosci

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Chemotherapy directly targets the transformed tumor cell, and has long been a key component of therapy for most early and advanced cancers. However, its utility is ultimately limited by unavoidable toxicity to normal tissues, and by drug resistance pathways deeply embedded within the biology of the tumor cell itself. These limitations strongly argue for innovative strategies to treat and manage cancer. Engaging the power of the patient's own immune system is a highly attractive way to complement the activity of standard cancer treatment. Tumor vaccines offer the potential for preventing cancer in those at high risk for disease development, preventing relapse in those diagnosed with early cancer, and treating advanced disease. Notably, the barriers to tumor vaccine efficacy are distinct from the limitations of combination chemotherapy. The ability of vaccines to induce a response robust enough to mediate tumor rejection is limited by the extent of disease burden, the suppressive effect of the local tumor micronenvironment, and multiple layers of systemic immune tolerance established to keep the immune response turned off. Chemotherapy can be used with tumor vaccines in unexpected ways, breaking down these barriers and unleashing the full potential of the antitumor immune response. KeywordsTRAIL; CEA; rVV; PSA; GM-CSF; CTL; TLR; LPS; Tumor Immunity; Chemotherapy; Cancer Vaccines; Immune Tolerance; Review INTRODUCTIONCurrent cancer therapies are limited either by local modes of action that fail to eradicate distant disease, or by inherent drug resistance integral to the biology of the transformed tumor cell. Many years of refining traditional modes of therapy have maximized their efficacy, but further therapeutic gains of significance are unlikely. More recently, biologically targeted drugs that precisely interrupt signaling pathways indispensable for tumor growth and progression have produced substantial improvement. As examples, the use of Trastuzumab to treat HER-2/neu-overexpressing breast cancer (1) and Imatinib to manage chronic myelogenous leukemia (2) greatly improve patient outcomes. Despite their promise, even precisely targeted therapeutics will ultimately be limited by drug resistance, resulting in disease relapse. This limitation of therapies that target the tumor cell itself is a call for the development of cancer therapies that work in a fundamentally different way. Tumor vaccines can recruit the power of the patient's own immune system to actively seek out and destroy transformed tumor cells, and represent a potentially potent complement to standard cancer therapies. Immune-based therapy has a higher level target than the tumor cell itself, re-tooling the host-tumor interaction to induce host cells that favor tumor rejection. Additional unique features of immune-based therapy make it even more attractive. Tumor vaccines can potentially induce a durable antitumor effect by virtue of the immunologic memory response, even in the absence of continued therapy. This memory response also defines im...

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Section: Chemotherapy and The Host Immunologic Milieumentioning

confidence: 93%

Chemotherapy and tumor immunity: an unexpected collaboration

Emens

2008

Front Biosci

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“…Furthermore, not all chemotherapeutic agents are compatible with vaccine. And finally, when combining vaccine with chemotherapy, dose scheduling can be critical [25,35,36]. More studies are needed to optimize the combined use of vaccine and chemotherapy.…”

Section: Vaccine and Chemotherapymentioning

confidence: 99%

Enhancing efficacy of therapeutic vaccinations by combination with other modalities

Gulley

Madan

Arlen

2007

Vaccine

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Novel strategies are emerging from preclinical and clinical investigations for combining vaccines with conventional and experimental anticancer therapies. Several lines of research show that combining either radiation or certain chemotherapeutic agents with vaccine can alter the phenotype of tumor cells, rendering them more susceptible to T-cell-mediated killing. Furthermore, there is emerging data suggesting that an immune response elicited by vaccine may augment the antitumor effectiveness of subsequent therapies. This article reviews and discusses therapeutic cancer strategies that employ vaccines sequentially or in combination with conventional cytotoxic therapies such as local radiation, chemotherapy, and hormone therapy, or immunopotentiating therapies such as anti-CTLA-4 monoclonal antibodies. Preliminary results of clinical studies using these combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and evidence of improved overall survival. Large randomized studies are currently underway to further investigate these findings.

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“…27,28 In fact, in one such model, an analysis of nine commonly used anti-neoplastic agents combined with GM-CSF-transduced tumor cell vaccines demonstrated improvement in the cure rate achieved with drug-vaccine combinations over that obtained with either modality alone. 29 In this study, the sequence and intervals of drug/vaccine administration proved to be critical parameters effecting outcome. To date, a detailed examination of phenotypic and functional immunologic recovery following standard therapy for AML has not been reported.…”

Section: Issues Of Tumor Burden Tolerance Andmentioning

confidence: 99%

New Developments in the Therapy of Acute Myelocytic Leukemia

Gorin¹

2000

Hematology

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In Section IV, Dr. Slavin reviews the concept of delivering non-myeloablative stem cell transplantation (NST) and delayed lymphocyte infusion (DLI) to increase tolerance in particular in high risk and older patients, and take advantage of the graftversus-leukemia (GVL) effect.All these approaches hold promise in reducing morbidity and mortality and differ from the older concepts aiming at delivering the highest possible doses of chemotherapy and/or total body irradiation to reach maximum leukemia cell kill, whatever the toxicity to the patient.

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Immunomodulatory properties of antineoplastic drugs administered in conjunction with GM-CSF-secreting cancer cell vaccines.

Cited by 30 publications

References 0 publications

Chemotherapy and tumor immunity: an unexpected collaboration

Chemotherapy and tumor immunity: an unexpected collaboration

Enhancing efficacy of therapeutic vaccinations by combination with other modalities

New Developments in the Therapy of Acute Myelocytic Leukemia

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