Designing Vaccines to Prevent Breast Cancer Recurrence or Invasive Disease

Stanton, Sasha E.; Disis, Mary L.

doi:10.2217/imt.15.5

Cited by 9 publications

(7 citation statements)

References 21 publications

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“…This pilot study is one of several recent or ongoing vaccine studies administered in the post-surgical adjuvant setting. Our peptide vaccine appears to be tolerable in this adjuvant setting, in agreement with other vaccine studies in the adjuvant setting (as opposed to the metastatic setting) [ 69 ]. Several peptides were immunogenic in this breast cancer population.…”

Section: Discussionsupporting

confidence: 86%

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

Dillon

Petroni

Smolkin

et al. 2017

j. immunotherapy cancer

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BackgroundBreast 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.MethodsA 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.ResultsTwelve 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.ConclusionsPeptide 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 Electronic supplementary materialThe online version of this article (10.1186/s40425-017-0295-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 86%

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

Dillon

Petroni

Smolkin

et al. 2017

j. immunotherapy cancer

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“…In addition, traditional therapy, including surgery, radiation, and chemotherapy, often cause various side effects and fail to remove the tumor completely [2]. Immunotherapy is a promising approach to treating patients with invasive and metastatic BC [3,4]. However, the immunosuppressive microenvironments induced by regulatory T cells (Treg) in BC present major barriers to successful antitumor immunotherapy [3,4].…”

mentioning

confidence: 99%

Regulatory T cells are an important prognostic factor in breast cancer: a systematic review and meta-analysis

Y¹,

Sun²,

Zheng³

et al. 2016

neo

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The clinical relevance of regulatory T cell (Treg) infiltration in breast cancer (BC) remains controversial, and no recent meta-analysis has been published on this subject. Our aim was to identify the precise relationship between Tregs and the prognosis and clinic-pathological features of BC. Eligible articles were identified with a MEDLINE database search over a period up to March 2015. Our meta-analysis was performed using STATA software 11.0 and Review Manager 5.3. The correlations between Treg infiltration and clinico-pathological features and BC prognosis were analyzed. Subgroup and sensitivity analyses, as well as meta-regression, were conducted. Eighteen published studies (including 8,562 patients) were eligible. Overall survival (OS) and disease-, recurrence-, and progression-free survival (DFS/RFS/PFS) were correlated with Treg infiltration (OR=2.03 (95% CI, 1.40-2.95; P=0.000) and 1.48 (95% CI, 1.00-2.19; P=0.050), respectively), including 3-, 5-, and 10-year mortality rates. In addition, low Treg infiltration was present in estrogen receptor (ER)-positive tumors (P=0.000), progesterone receptor (PR)-positive tumors (P=0.003), Her2-negative tumors (P=0.000) and histological grade I/II tumors (P=0.001). No publication bias was observed with the exception of OS. Subgroup analysis suggested that the mortality rate of the high Treg infiltration subgroup was increased compared with the low Treg infiltration subgroup among ER-positive patients. Treg infiltration indicated a poorer prognosis for BC and is related to ER, PR, and Her2 status and histological grade. Thus, Treg infiltration could help predict outcomes and guide clinical therapy.

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“…Presently, “therapeutic” is the operative word as the application of individual neoantigens to cancer immunoprevention is not yet a reality. However, sequencing could be translated into new approaches to secondary and tertiary immunoprevention in which individual tumor antigens, discovered in preneoplastic, early neoplastic, or primary lesions, can then be targeted with specific vaccines [ 123 , 124 ].…”

Section: Target Antigens For Cancer Immunoprevention: Drivers or Pmentioning

confidence: 99%

The Promise of Preventive Cancer Vaccines

2015

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Years of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While true primary cancer prevention is still but a long-term goal, secondary and tertiary prevention are already in the clinic and providing encouraging results. A combination of immunopreventive cancer strategies and recently approved checkpoint inhibitors is a further promise of forthcoming successful cancer disease control, but prevention will require a considerable reduction of currently reported toxicities. These considerations summed with the increased understanding of tumor antigens allow space for an optimistic view of the future.

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Designing Vaccines to Prevent Breast Cancer Recurrence or Invasive Disease

Cited by 9 publications

References 21 publications

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

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

Regulatory T cells are an important prognostic factor in breast cancer: a systematic review and meta-analysis

The Promise of Preventive Cancer Vaccines

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