Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities.
| Title: | Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities. |
|---|---|
| Authors: | Shemesh CS; Department of Clinical Pharmacology Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: shemesh.colby@gene.com.; Hsu JC; Department of Clinical Pharmacology Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.; Hosseini I; Department of Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.; Shen BQ; Department of Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.; Rotte A; Department of Clinical Pharmacology Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.; Twomey P; Department of Product Development Safety, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.; Girish S; Department of Clinical Pharmacology Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.; Wu B; Department of Clinical Pharmacology Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. |
| Source: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2021 Feb 03; Vol. 29 (2), pp. 555-570. Date of Electronic Publication: 2020 Sep 30. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't; Review |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2017- : Cambridge, MA : Cell Press; Original Publication: San Diego, CA : Academic Press, 2000- |
| MeSH Terms: | Immunotherapy*/methods; Cancer Vaccines/*immunology ; Cancer Vaccines/*therapeutic use ; Neoplasms/*immunology ; Neoplasms/*therapy; Antigens, Neoplasm/immunology ; Antigens, Neoplasm/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Precision Medicine/methods ; T-Lymphocytes/immunology ; Biomarkers, Tumor ; Clinical Trials as Topic ; Drug Development ; Humans |
| Abstract: | Tremendous innovation is underway among a rapidly expanding repertoire of promising personalized immune-based treatments. Therapeutic cancer vaccines (TCVs) are attractive systemic immunotherapies that activate and expand antigen-specific CD8+ and CD4+ T cells to enhance anti-tumor immunity. Our review highlights key issues impacting TCVs in clinical practice and reports on progress in development. We review the mechanism of action, immune-monitoring, dosing strategies, combinations, obstacles, and regulation of cancer vaccines. Most trials of personalized TCVs are ongoing and represent diverse platforms with predominantly early investigations of mRNA, DNA, or peptide-based targeting strategies against neoantigens in solid tumors, with many in combination immunotherapies. Multiple delivery systems, routes of administration, and dosing strategies are used. Intravenous or intramuscular administration is common, including delivery by lipid nanoparticles. Absorption and biodistribution impact antigen uptake, expression, and presentation, affecting the strength, speed, and duration of immune response. The emerging trials illustrate the complexity of developing this class of innovative immunotherapies. Methodical testing of the multiple potential factors influencing immune responses, as well as refined quantitative methodologies to facilitate optimal dosing strategies, could help resolve uncertainty of therapeutic approaches. To increase the likelihood of success in bringing these medicines to patients, several unique development challenges must be overcome.; (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.) |
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| Contributed Indexing: | Keywords: adjuvant; cancer immunotherapy; clinical pharmacology; clinical trials; drug development; personalized therapeutic cancer vaccine; tumor neoantigen |
| Substance Nomenclature: | 0 (Antigens, Neoplasm); 0 (Biomarkers, Tumor); 0 (Cancer Vaccines) |
| Entry Date(s): | Date Created: 20201010 Date Completed: 20211018 Latest Revision: 20220204 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7854282 |
| DOI: | 10.1016/j.ymthe.2020.09.038 |
| PMID: | 33038322 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't; Review