AE37: a novel T-cell-eliciting vaccine for breast cancer

Sears, Alan K.; Perez, Sonia A.; Clifton, Guy T.; Benavides, Linda C.; Gates, Jeremy D.; Clive, Kevin S.; Holmes, Jarrod P.; Shumway, Nathan M.; Echo, David C. Van; Carmichael, Mark G.; Ponniah, Sathibalan; Baxevanis, Constantin N.; Mittendorf, Elizabeth A.; Papamichail, Michael; Peoples, George E.

doi:10.1517/14712598.2011.616889

Cited by 45 publications

(21 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The vaccine was found to be safe and well tolerated, and demonstrated benefits in patients with HER2 non-over expressing tumours, especially those with triple negative disease, where the 5-year relative risk reduction for recurrence reached 35%. In a separate sub study conducted in our laboratory, we found that pre-existing immunity either as in vitro (levels of IFNγ) or in vivo (dermal reaction) parameter, might serve as a predictive biomarker for clinical response in patients vaccinated with AE37 [74][75][76]. …”

Section: The Ae37 Therapeutic Cancer Vaccine Paradigmmentioning

confidence: 92%

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer

Pistamaltzian

Perez

Baxevanis

2016

Forum of Clinical Oncology

View full text Add to dashboard Cite

There is now increasing evidence to suggest that adaptive immunity plays a major role in regulating the growth of tumour cells. T cells play a major role in coordinating the immune response against tumourspecific antigens during tumour progression. While T cell activation depends on the initial tumour antigen-specific signal provided to the T cell receptors via the antigenloaded major histocompatibility complex (MHC) complex on dendritic cells (DCs), additional signals provided by costimulatory molecules fine-tune this response, determining its strength, nature and duration. To this end, the discovery of receptors regulating T cell activation against the autologous tumour was of paramount importance for understanding how cancer progresses under immunosurveillance. The CD28 co-receptor acts as a strong positive costimulatory receptor, and CTL antigen-4 (CTLA-4) as a potent co-inhibitory receptor. The programmed death 1 (PD-1) receptor: PD-Ligand (PD-L) pathway is another major receptor-ligand network that functions primarily to provide a co-inhibitory signal. PD1: PD-L interactions maintain peripheral tolerance and are exploited by tumours to evade immune eradication by memory T cells specifically recognizing tumour peptides [1]. As such, this pathway has emerged as a potential therapeutic target for enhancing the immune response. A second important discovery, which also sheds light to our understanding of tumour evolution, is presented by the "immunoediting" theory. According to this theory, the immune system "edits" the tumour immunogenicity, resulting in the promotion or suppression of tumour growth, a phenomenon [2]. As a result of its capacity to shape tumour immunogenicity, an additional role for the immune system has emerged, namely that of prognostic indicator. Studies by Galon et al. [3], initiated almost a decade ago, have demonstrated that the quantity, quality and spatial distribution of immune cells within the tumour has a greater prognostic value than the standard tumour staging based on tumour burden, infiltration of draining and regional lymph nodes by tumour cells, and evidence of metastases. This so-called "immunoscore" came to complete the immunoediting theory by increasing the knowledge of the immune events inside the tumours, and by better understanding, the immune architecture of these tumours, as well as the functional programs of their constituents, all of which complete the idea of how tumours evade from immunosurveillance. Forum of Clinical OncologyReinstating endogenous antitumor immunity: The concept of therapeutic management of cancer * E-mail: nfpist73@yahoo.gr However, a lot of cancer patients will fail to respond and therefore, it becomes crucial to identify biomarkers to predict who of the patients will most likely benefit from these therapies. Abstract: © De Gruyter Open Keywords: Cancer immunotherapy • Tumor infiltrating lymphocytes • Immunoscore • Cancer vaccines • Checkpoint inhibitors

show abstract

Section: The Ae37 Therapeutic Cancer Vaccine Paradigmmentioning

confidence: 92%

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer

Pistamaltzian

Perez

Baxevanis

2016

Forum of Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…This may be due to the heavy tumor burden which generates a hostile tumor microenvironment with a plethora of suppressor elements dampening antitumor responses. To circumvent this issue, recent clinical trials were performed with patients at the adjuvant setting with minimal residual disease and a high risk of relapse [14]. The rationale behind vaccination in this clinical setting is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses.…”

Section: Cancer Vaccines: Limited Success But the Research Should Remmentioning

confidence: 99%

Cancer vaccines: limited success but the research should remain viable

Baxevanis

Perez

2016

Expert Review of Vaccines

View full text Add to dashboard Cite

“…These moved into early-phase clinical studies in the first decade of the 2000s including: several early-phase clinical studies of the immunodominant E75 peptide with granulocyte macrophage colony-stimulating factor as a biological adjuvant (now referred to as NeuVax™) [221][222][223]; of an improved E75 vaccine, AE37 (NCT00524277) [224][225][226][227]; and of the subdominant G2 peptide (NCT00524277) [228][229][230]. Other groups have ongoing Phase I and II clinical studies examining other peptides, other adjuvants and/or combinations of immunomodulatory agents (NCT00058526, NCT00194714, NCT00791037, NCT00952692, NCT01355393, NCT01376505 and NCT01632332).…”

Section: Her2/neu Antigen-specific Immunotherapymentioning

confidence: 99%

HER2/neu: an increasingly important therapeutic target. Part 1: basic biology & therapeutic armamentarium

Nelson¹

2014

Clinical Investigation

View full text Add to dashboard Cite

AE37: a novel T-cell-eliciting vaccine for breast cancer

Cited by 45 publications

References 27 publications

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer

Cancer vaccines: limited success but the research should remain viable

HER2/neu: an increasingly important therapeutic target. Part 1: basic biology & therapeutic armamentarium

Contact Info

Product

Resources

About