Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine.
OBJECTIVE
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 patient's 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 patient's 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.
Abou-Alfa
Ghassan K
GK
Department of Internal Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. abou-alg@mskcc.org
Chapman
Paul B
PB
Feilchenfeldt
Jonas
J
Brennan
Murray F
MF
Capanu
Marinela
M
Gansukh
Bolorsukh
B
Jacobs
Gria
G
Levin
Adrah
A
Neville
Deirdre
D
Kelsen
David P
DP
O'Reilly
Eileen M
EM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000601:surgery; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D004334:Drug Administration Schedule; D058501:Enzyme-Linked Immunospot Assay; D005240:Feasibility Studies; D005260:Female; D011905:Genes, ras / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000276:immunology*; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor