Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients

Berinstein, Neil L.; Karkada, Mohan; Oza, Amit M.; Odunsi, Kunle; Villella, Jeannine; Nemunaitis, John; Morse, Michael A.; Pejović, Tanja; Bentley, J.; Buyse, Marc; Nigam, Rita; Weir, Genevieve; MacDonald, Lisa; Quinton, Tara; Rajagopalan, Rajkannan; Sharp, Kendall; Penwell, Andrea; Sammatur, Leeladhar; Burzykowski, Tomasz; Stanford, Marianne M.; Mansour, Marc

doi:10.1080/2162402x.2015.1026529

Cited by 81 publications

(78 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DPX-based cancer immunotherapeutics are currently in Phase 2 clinical development [35, 36]. The changes in lymph node volume we observed were unique to vaccinated mice, and likely indicative of clonal expansion of effector T-cells, previously demonstrated with DPX vaccines [37].…”

Section: Introductionmentioning

confidence: 52%

Using lymph node swelling as a potential biomarker for successful vaccination

Brewer¹,

DeBay²,

Dude³

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

There is currently a lack of biomarkers to help properly assess novel immunotherapies at both the preclinical and clinical stages of development. Recent work done by our group indicated significant volume changes in the vaccine draining right lymph node (RLN) volumes of mice that had been vaccinated with DepoVaxTM, a lipid-based vaccine platform that was developed to enhance the potency of peptide-based vaccines. These changes in lymph node (LN) volume were unique to vaccinated mice.To better assess the potential of volumetric LN markers for multiple vaccination platforms, we evaluated 100 tumor bearing mice and assessed their response to vaccination with either a DepoVax based vaccine (DPX) or a water–in-oil emulsion (w/o), and compared them to untreated controls. MRI was used to longitudinally monitor LN and tumor volumes weekly over 4 weeks. We then evaluated changes in LN volumes occurring in response to therapy as a potential predictive biomarker for treatment success.We found that for both vaccine types, DPX and w/o, the %RLN volumetric increase over baseline and the ratio of RLN/LLN were strong predictors of successful tumor suppression (LLN is left inguinal LN). The area under the curve (AUC) was greatest, between 0.75-0.85, two (%RLN) or three (RLN/LLN) weeks post-vaccination. For optimized critical thresholds we found these biomarkers consistently had sensitivity >90% and specificity >70% indicating strong prognostic potential. Vaccination with DepoVax had a more pronounced effect on draining lymph nodes than w/o emulsion vaccines, which correlated with a higher anti-tumor activity in DPX-treated mice.

show abstract

Section: Introductionmentioning

confidence: 52%

Using lymph node swelling as a potential biomarker for successful vaccination

Brewer¹,

DeBay²,

Dude³

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

show abstract

“…297,309,310 Accumulating evidence suggest indeed that metronomic chemotherapy and hypofractionated radiation (rather than chemotherapy at the MTD and high single-dose radiation) exerts superior immunostimulatory (and hence therapeutic, at least in some settings) effects. [311][312][313][314] Alongside, it will be important to devise highly efficient combinatorial regimens that harness not only the ability of some treatments to drive ICD, but also the off-target immunostimulatory effects of a variety of agents. We are convinced that conventional therapeutic regimens -if properly employed -are a very powerful and relatively economical tool to drive clinically relevant anticancer immune responses.…”

Section: Discussionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

View full text Add to dashboard Cite

The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

show abstract

“…Concurrent administration of metronomic doses of cyclophosphamide in combination with an HLA class I-binding survivin peptide vaccine (DPX-Survivac) increased the antigen-specific immune response. This was associated with the differentiation of naïve T-cells into central/effector memory cells (CM/ EM) and late differentiated poly-functional antigen-specific CD8 + T-cells in advanced ovarian cancer patients [76]. Similarly, metronomic administration of a high dose cocktail of chemotherapeutic agents (including cyclophosphamide, paclitaxel and docetaxel) during vaccination with a multi-peptide cocktail of peptides (comprising hepatitis C virus-derived antigens and tumor-associated antigens) resulted in an enhanced specific T-cell response and a reduced Treg frequency in hepatocellular carcinoma (HCC) patients [79].…”

Section: Simultaneous Combination Of Chemotherapy With Vaccination Inmentioning

confidence: 99%

The importance of correctly timing cancer immunotherapy

Nejad

Welters

Arens

et al. 2016

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Introduction:The treatment options for cancer-surgery, radiotherapy and chemotherapy-are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other's shortcomings. Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific Tcells but also to support and enhance their anti-tumor efficacy. Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities. ARTICLE HISTORY

show abstract

Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients

Cited by 81 publications

References 35 publications

Using lymph node swelling as a potential biomarker for successful vaccination

Using lymph node swelling as a potential biomarker for successful vaccination

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

The importance of correctly timing cancer immunotherapy

Contact Info

Product

Resources

About