A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling.

PURPOSE: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab-mediated immune modulation in women with operable breast cancer. EXPERIMENTAL DESIGN: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy. Exploratory studies of immune activation were performed on peripheral blood and tumor. RESULTS: Preoperative cryoablation and/or ipilimumab were safe and tolerable, with no delays in pre-planned surgery. Grade III toxicity was seen in 1 of 19 (unrelated rash after ipilimumab). Combination therapy was associated with sustained peripheral elevations in: Th1-type cytokines, activated (ICOS+) and proliferating (Ki67+) CD4+ and CD8+ T cells, and posttreatment proliferative T-effector cells relative to T-regulatory cells within tumor. CONCLUSIONS: Preoperative cryoablation and single-dose ipilimumab are safe alone or in combination with no surgical delays incurred. Potentially favorable intratumoral and systemic immunologic effects were observed with the combination, suggesting the possibility for induced and synergistic antitumor immunity with this strategy. Clin Cancer Res; 22(23); 5729-37. ©2016 AACR.

Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine.

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 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.