Development of Cancer Vaccine and Targeted Immune Checkpoint Therapies

2017 ◽  
pp. 225-241
Author(s):  
Yuwen Zhu ◽  
Alessandro Paniccia ◽  
Barish H. Edil ◽  
Richard D. Schulick
Keyword(s):  
Cancer Vaccine ◽  
Immune Checkpoint

Combination of a therapeutic cancer vaccine and immune checkpoint inhibitors in prostate cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 5084-5084 ◽  
Author(s):  
Ravi Amrit Madan ◽  
Marijo Bilusic ◽  
Julius Strauss ◽  
Fatima Karzai ◽  
Lisa M. Cordes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Cancer Vaccine

scholarly journals PD-1 Immune Checkpoint Blockade Promotes Therapeutic Cancer Vaccine to Eradicate Lung Cancer

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 317 ◽  
Author(s):  
Pournima Kadam ◽  
Sherven Sharma
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Tumor Burden ◽  
Tumor Lysate ◽  
Therapeutic Cancer Vaccine ◽  
Tumor Eradication

(1) Background: Targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the activation of immune responses against cancer. Therapeutic vaccination, which induces specific immune responses against tumor antigens (Ags), is an attractive option. (2) Methods: Utilizing a K-RasG12Dp53null murine lung cancer model we determined tumor burden, tumor-infiltrating T cell (TIL) cytolysis, immunohistochemistry, flow cytometry, and CD4 and CD8 depletion to evaluate the efficacy of PD-1 blockade combined with CCL21-DC tumor lysate vaccine. (3) Results: Anti-PD-1 plus CCL21-DC tumor lysate vaccine administered to mice bearing established tumors (150 mm3) increased expression of perforin and granzyme B in the tumor microenvironment (TME), increased tumor-infiltrating T cell (TIL) activity, and caused 80% tumor eradication. Mice with treatment-induced tumor eradication developed immunological memory, enabling tumor rejection upon challenge and cancer-recurrence-free survival. The depletion of CD4 or CD8 abrogated the antitumor activity of combined therapy. PD-1 blockade or CCL21-DC tumor lysate vaccine monotherapy reduced tumor burden without tumor eradication. (4) Conclusion: Immune checkpoint blockade promotes the activity of the therapeutic cancer vaccine. PD-1 blockade plus CCL21-DC tumor lysate vaccine therapy could benefit lung cancer patients.

scholarly journals A personalized anti-cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella

2021 ◽  
Author(s):  
Erkko Ylosmaki ◽  
Manlio Fusciello ◽  
Arttu Uoti ◽  
Sara Feola ◽  
Beatriz Martins ◽  
...  
Keyword(s):  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Cell ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Mmr Vaccine ◽  
Vaccine Platform ◽  
Anti Cancer ◽  
Checkpoint Inhibitor Therapy

Common vaccines for infectious diseases have been repurposed as cancer immunotherapies. Intratumoural administration of these repurposed vaccines can induce immune cell infiltration into the treated tumour. Here, we have used an approved trivalent live attenuated measles, mumps, and rubella (MMR) vaccine in our previously developed PeptiENV anti-cancer vaccine platform. Intratumoural administration of this novel MMR-containing PeptiENV anti-cancer vaccine significantly increased both intratumoural as well as systemic tumour-specific T cell responses. In addition, PeptiENV therapy, in combination with immune checkpoint inhibitor therapy, significantly improved tumour growth control and survival as well as increased the number of mice responsive to immune checkpoint inhibitor therapy.

scholarly journals Intron retention as a novel source of cancer neoantigens

2018 ◽  
Author(s):  
Alicia C. Smart ◽  
Claire A. Margolis ◽  
Harold Pimentel ◽  
Meng Xiao He ◽  
Diana Miao ◽  
...  
Keyword(s):  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Vaccine Development ◽  
Intron Retention ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Sequencing Data ◽  
Transcriptional Dysregulation ◽  
Retained Intron ◽  
Personalized Cancer

Personalized cancer vaccine strategies directed at tumor neoantigens derived from somatic mutations in the DNA are currently under prospective evaluation1, 2. Alterations in tumor RNA, rather than DNA, may also represent a previously-unexplored source of neoantigens. Here, we show that intron retention, a widespread feature of cancer transcriptomes3, 4, represents a novel source of tumor neoantigens. We developed an in silico approach to identify retained intron neoantigens from RNA sequencing data and applied this methodology to tumor samples from patients with melanoma treated with immune checkpoint blockade5, 6, discovering that the retained intron neoantigen burden in these samples augments the DNA-derived, somatic neoantigen burden. We validated the existence of retained intron derived neoantigens by implementing this technique on cancer cell lines with mass spectrometry-derived immunopeptidome data7, 8, revealing that retained intron neoantigens were complexed with MHC I experimentally. Unexpectedly, we observed a trend toward lack of clinical benefit from immune checkpoint blockade in high retained intron load-tumors, which harbored transcriptional signatures consistent with cell cycle dysregulation and DNA damage repair. Our results demonstrate the contribution of transcriptional dysregulation to the overall burden of tumor neoantigens, provide a foundation for augmenting personalized cancer vaccine development with a new class of tumor neoantigens, and demonstrate how global transcriptional dysregulation may impact selective response to immune checkpoint blockade.Statement of significanceWe developed and experimentally validated a computational pipeline to identify a novel class of tumor neoantigens derived from RNA-based intron retention, which is prevalent throughout cancer transcriptomes. The discovery of transcriptionally-derived tumor neoantigens expands the tumor immunopeptidome and contributes potential substrates for personalized cancer vaccine development.

scholarly journals Cancer vaccine: learning lessons from immune checkpoint inhibitors

2018 ◽  
Vol 9 (2) ◽  
pp. 263-268 ◽  
Author(s):  
ZhenLong Ye ◽  
Qiming Qian ◽  
HuaJun Jin ◽  
QiJun Qian
Keyword(s):  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

scholarly journals Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Alessandra Lopes ◽  
Kevin Vanvarenberg ◽  
Špela Kos ◽  
Sophie Lucas ◽  
Didier Colau ◽  
...  
Keyword(s):  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Antitumor Immunity ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
P815 Mastocytoma
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