A pilot study of the immunogenicity of a 9-peptide breast cancer vaccine plus poly-ICLC in early stage breast cancer.

BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid. The vaccine was administered on days 1, 8, 15, 36, 57, 78. CD8+ T cell responses to the vaccine were assessed by both direct and stimulated interferon gamma ELIspot assays. RESULTS: Twelve patients with breast cancer were treated: five had estrogen receptor positive disease and five were HER2 amplified. There were no dose-limiting toxicities. Toxicities were limited to Grade 1 and Grade 2 and included mild injection site reactions and flu-like symptoms, which occurred in most patients. The most common toxicities were injection site reaction/induration and fatigue, which were experienced by 100% and 92% of participants, respectively. In the stimulated ELIspot assays, peptide-specific CD8+ T cell responses were detected in 4 of 11 evaluable patients. Two patients had borderline immune responses to the vaccine. The two peptides derived from CEA were immunogenic. No difference in immune response was evident between patients receiving endocrine therapy and those not receiving endocrine therapy during the vaccine series. CONCLUSIONS: Peptide vaccine administered in the adjuvant breast cancer setting was safe and feasible. The TLR3 adjuvant, poly-ICLC, plus helper peptide mixture provided modest immune stimulation. Further optimization is required for this multi-peptide vaccine/adjuvant combination. TRIAL REGISTRATION: ClinicalTrials.gov (posted 2/15/2012): NCT01532960. Registered 2/8/2012. https://clinicaltrials.gov/show/NCT01532960.

Survivorship Care Plans: Rural, Low-Income Breast Cancer Survivor Perspectives.

BACKGROUND: Despite increasing implementation of survivorship care plans (SCPs), cancer survivors still experience unmet needs post-treatment. Rural, low-income survivors experience less planning for supportive care during treatment, which is difficult to overcome after patients complete treatment.
. OBJECTIVES: This pilot study explores post-treatment survivorship care planning execution, perception, and needs among rural, low-income cancer survivors. 
. METHODS: A longitudinal, descriptive, qualitative design with semistructured interviews was used. 
. FINDINGS: Rural survivors' responses reflected lack of knowledge about post-treatment care, including how to assess for cancer recurrence. Delivery of the SCP during the final treatment appointment was inadequate for knowledge retention. Individualized assessment of survivorship needs and education post-treatment may improve long-term health outcomes for this population.

Immunogenicity for CD8+ and CD4+ T cells of 2 formulations of an incomplete freund's adjuvant for multipeptide melanoma vaccines.

An incomplete Freund's adjuvant (IFA) commonly used in experimental cancer vaccines has recently been reformulated. Oleic acid used in the surfactant was purified from a vegetable source (olives, IFA-VG) rather than an animal source (beef tallow, IFA-AN). To provide an insight into the adjuvant properties of the new formulation, we reviewed T-cell responses, by enzyme-linked immunospot assay, to multipeptide vaccines in 2 sequential clinical trials that spanned this transition of adjuvants. Analyses included 194 patients who received either IFA-AN or IFA-VG for all vaccines, and a subset of 93 patients best matched by study arm for vaccine antigens (12 melanoma peptides restricted by major histocompatibility complex class I, 12MP; plus a tetanus helper peptide, tet) administered with IFA but without granulocyte macrophage-colony stimulating factor. Inflammation was observed at vaccine sites clinically for almost all patients, even including ulceration in a subset with each IFA formulation. CD8 T-cell response rates to the 12 melanoma peptides were 53% [95% confidence interval (CI), 44%, 61%)] for IFA-AN and 46% [95% CI, 32%, 59%)] for IFA-VG. In the 93 patient subset, these rates were 73% [95% CI, 61%, 83%)] and 70% [95% CI, 47%, 87%)], respectively. CD4 T-cell responses to tetanus helper peptide were identified in 94% [95% CI, 86%, 98%)] and 96% [95% CI, 78%, 100%)], respectively. Responses to individual human leukocyte antigen (HLA)-A1, A2, and DR associated peptides were largely preserved, but reactivity trended lower for some HLA-A3 associated peptides. Despite the necessarily retrospective nature of the analysis and limitations of multiple comparisons, our summary data support the use of IFA-VG as an adjuvant with multipeptide vaccines in melanoma patients.

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer.

Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who were human leukocyte antigen (HLA)-A1, HLA-A2, or HLA-A3, were eligible to enroll in a phase 1 study designed to assess the safety and immunogenicity of a peptide-based vaccine. Participants received 5 class I major histocompatibility complex-restricted synthetic peptides derived from multiple ovarian cancer-associated proteins plus a class II major histocompatibility complex-restricted synthetic helper peptide derived from tetanus toxoid protein. The vaccines were administered with granulocyte macrophage-colony stimulating factor in Montanide ISA-51 adjuvant over a 7-week period. All vaccine-related toxicities were grade 1 to 2, the most common being injection site reaction (grade 2, 100%), fatigue (grade 1, 78%), and headache (grade 1, 67%). Lymphocytes from the peripheral blood and a node draining a secondary vaccine site (sentinel immunized node) were harvested during the course of vaccination and T-cell responses to the peptides were evaluated using an enzyme-linked immunosorbent spot assay. CD8 T-cell responses were detected in 1 participant ex vivo and in 8 of 9 participants (89%) after in vitro stimulation. All 4 HLA-A2 and HLA-A3-restricted peptides were immunogenic. This includes 2 peptides, folate binding protein (FBP191-199) and Her-2/neu754-762, which had not previously been evaluated in vaccines in humans. Responding T cells required over 200 nM for half-maximal reactivity. These data support continued investigation of these peptides as immunogens for patients with ovarian cancer but, owing to low potency, also suggest a need for additional immunomodulation in combination with vaccines to increase the magnitude and to improve the quality of the T-cell responses.