Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine Journal Article
| Authors: | Abou-Alfa, G. K.; Chapman, P. B.; Feilchenfeldt, J.; Brennan, M. F.; Capanu, M.; Gansukh, B.; Jacobs, G.; Levin, A.; Neville, D.; Kelsen, D. P.; O'Reilly, E. M. |
| Article Title: | Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine |
| Abstract: | Purpose: Codon 12 mutations of K-ras are frequent in pancreatic adenocarcinoma, and represent potential tumor-specific neoantigens. The objective of this study was to assess the safety and efficacy of immunizing patients with resected pancreatic cancer with a vaccine targeted against their tumor-specific K-ras mutation. Methods: Patients with resected pancreatic cancer, with K-ras mutations at codon 12, were vaccinated once monthly for 3 months with a 21-mer peptide vaccine containing the corresponding K-ras mutation of the patients tumor. About 200 μg of peptide vaccine was injected intradermally on day 7 of a 10-day course of intradermal granulocyte macrophage colony-stimulating factor. Toxicity was assessed by National Cancer Institute Common Toxicity Criteria v2.0. Immune responses were evaluated by delayed-type hypersensitivity (DTH) tests and the enzyme-linked immunosorbent spot assays. Results: Of 62 screened patients, 24 were vaccinated. There were no grade 3-5 vaccine-specific toxicities. The only National Cancer Institute grade 1 and 2 toxicity was erythema at the injection site (94%). Nine patients (25%) were evaluable for immunologic responses. One patient (11%) had a detectable immune response specific to the patients K-ras mutation, as assessed by DTH. Three patients (13%) displayed a DTH response that was not specific. Median recurrence free survival time was 8.6 months (95% confidence interval, 2.96-19.2) and median overall survival time was 20.3 months (95% confidence interval, 11.6-45.3). Conclusions: K-ras vaccination for patients with resectable pancreatic adenocarcinoma proved to be safe and tolerable with however no elicitable immunogenicity and unproven efficacy. Future development of adjuvant vaccine therapies should use more immunogenic vaccines. Copyright © 2011 by Lippincott Williams & Wilkins. |
| Keywords: | cancer chemotherapy; cancer survival; clinical article; aged; unclassified drug; gene mutation; overall survival; clinical trial; erlotinib; fluorouracil; drug efficacy; drug safety; gemcitabine; adjuvant therapy; cancer adjuvant therapy; nausea; vomiting; abdominal pain; survival time; cancer vaccine; cancer immunization; pancreas adenocarcinoma; tumor immunity; pancreatic cancer; peptide vaccine; k ras protein; injection site erythema; recombinant granulocyte macrophage colony stimulating factor; vaccine; k-ras; adjuvant; delayed hypersensitivity; ras12d peptide; ras12r peptide; ras12v peptide |
| Journal Title: | American Journal of Clinical Oncology |
| Volume: | 34 |
| Issue: | 3 |
| ISSN: | 0277-3732 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2011-06-01 |
| Start Page: | 321 |
| End Page: | 325 |
| Language: | English |
| DOI: | 10.1097/COC.0b013e3181e84b1f |
| PROVIDER: | scopus |
| PUBMED: | 20686403 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "CODEN: AJCOD" - "Source: Scopus" |
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