Synergy between chemotherapy and cancer vaccination

Sluis, Tetje C. van der; Burg, Sjoerd H. van der; Melief, Cornelis J.M.

doi:10.18632/aging.100752

Cited by 4 publications

(2 citation statements)

References 6 publications

(8 reference statements)

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“…Moreover, chemotherapy, such as by cisplatin, can also enhance responses to T cell based immune therapies by sensitizing the tumor cells to T cell-induced death rather than by ICD (34). For example, cisplatin has been shown to synergize with synthetic long peptide (SLP) vaccination and improve tumor-cell killing in a preclinical tumor model (35).…”

Section: Combinations With Stimulation Of Antigen Release and Danger mentioning

confidence: 99%

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

2016

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In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.

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Section: Combinations With Stimulation Of Antigen Release and Danger mentioning

confidence: 99%

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

2016

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“…Paralleling our ex vivo flow cytometric data, we observed that the in vivo efficacy of the E7-TriMix vaccine was the most limited in the genital tract. As synergy between chemotherapy and cancer vaccination is being increasingly emphasized, we addressed the possibility of combinatory therapy with E7-TriMix mRNA and cisplatin [13]. We observed a dramatic improvement in the quality of life of the treated mice during the course of the experiment, followed by a complete rejection of genitally located tumor lesions.…”

Section: Short Communicationmentioning

confidence: 96%

Improving Anti-cancer Immunotherapy by Simultaneous Targeting Suppressive Tumor Microenvironment

Bialkowski¹,

Thielemans²

2016

J Vaccines Vaccin

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Recent advances in immunotherapy led to a breakthrough in cancer treatment, changing the algorithms of clinical cancer management. Notwithstanding this success, numerous immune escape mechanisms significantly hamper the long-term efficacy of immunotherapy. A growing body of evidence recognizes immunosuppressive tumor microenvironment (TME) as a major obstacle for effective anti-cancer immunotherapy. It is therefore postulated that multiple pathways in TME need to be targeted in support to the induction of tumor-specific effector immune cells. Our lab has developed a novel mRNA vaccination platform allowing for induction of strong anti-tumor immune responses in the context of cervical cancer. In our recent study, using a variety of in vivo and ex vivo techniques, we observed the existence of organ-specific microenvironments that differed in their immunosuppressive capacity. We demonstrated that the particularly hostile nature of genital tract TME could be alleviated using cisplatin. This data indicated that the induction of tumor-specific T cells accompanied by a simultaneous targeting of TME is a prerequisite for the improvement of adaptive anti-cancer immunotherapies, thereby emphasizing the need for a TME-tailored immunotherapy.Keywords: Tumor microenvironment; Personalized immunotherapy; mRNA vaccine; Cisplatin Short CommunicationThe latest analyses of clinical success rates for drug development indicate a significant divergence between R&D expenses and new drug approvals. While anti-cancer drugs constitute a large majority of drug development paths, the 'Likelihood of Approval' rate for oncology (6.7%) is the lowest amongst all tested conditions [1]. One of the reasons for this status quo can be a limited predictive value of currently used animal models, particularly in the context of interactions between the host immune system and cancer cells. This can partly be due to the fact that traditionally the role of the host immune system was deemphasized giving the priority to the tumor cells [2]. As a consequence, for years the accurate recapitulation of the tumor microenvironment (TME) was underappreciated, disregarding the immune contexture as a powerful contributor to tumorigenesis [3]. Over decades, ectopically implanted tumor cell lines in syngeneic mice served as an universal model for anti-cancer drug evaluation [4]. Although such approach offered a unique possibility of in vivo therapy in the context of a fully functional immune system, the impact of the primary, orthotopic tumor location, and thus relevant microenvironment, was largely neglected. Only a few groups took the effort to compare the ectopic and orthotopic tumors side by side, but their groundbreaking findings did not reach the mainstream of anticancer research. For instance, it has been demonstrated that renal, colon and prostate tumors respond to immunotherapy to a much lesser extent in the orthotopic setting compared to the subcutaneous location [5]. In analogy, renal carcinoma cells were described to be more resistant to treatment...

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Synergy between chemotherapy and cancer vaccination

Cited by 4 publications

References 6 publications

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

Improving Anti-cancer Immunotherapy by Simultaneous Targeting Suppressive Tumor Microenvironment

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