A promising platform for predicting toxicity.

Organ-on-chip approaches could help researchers to better predict the toxicity of cancer immunotherapy drugs

A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer

phase i ii study of spartalizumab pdr001 an anti pd1 mab in patients with advanced melanoma or non small cell lung cancer

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PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate

Background: Abiraterone acetate (AA) is widely used in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, a significant percentage of patients will still progress, highlighting the need to identify patients more likely to benefit from AA. Parameters linked to prostate-specific antigen (PSA) kinetics are promising prognostic markers. We have examined clinical and PSA-related factors potentially asso- ciated with overall survival (OS) in patients treated with AA. Methods: Between 2011 and 2014, 104 patients with mCRPC treated with AA after progression to docetaxel at centers of the Catalan Institute of Oncology were included in this retrospective study. Patients were assessed monthly. Baseline characteristics and vari- ables related to PSA kinetics were included in univariate and multivariate analyses of OS. Results: Median OS was 16.4 months (range 12.4-20.6) for all patients. The univariate analysis identified the following baseline characteristics as significantly associated with OS: ECOG PS, location of metastases, time between starting androgen deprivation therapy and starting AA, time between stopping docetaxel treatment and starting AA, neutrophil- lymphocyte ratio (NLR), alkaline phosphatase levels, and PSA levels. Factors related to PSA kinetics associated with longer OS were PSA response >50%, early PSA response (>30% decline at four weeks), PSA decline >50% at week 12, PSA nadir 140 days, the combination of PSA nadir and time to PSA nadir, and low end-of- treatment PSA levels. The multivariate analysis identified ECOG PS (HR 37.46; p<0.001), NLR (HR 3.7; p<0.001), early PSA response (HR 1.22; p=0.002), and time to PSA nadir (HR 0.39; p=0.002) as independent prognostic markers. Conclusion: Our results indicate an association between PSA kinetics, especially early PSA response, and outcome to AA after progression to docetaxel. Taken together with other factors, lack of an early PSA response could identify patients who are unlikely to benefit from AA and who could be closely monitored with a view to offering alternative therapies

tumor infiltrating lymphocytes tils and pdl1 expression as prescreening enrichment biomarkers of clinical benefit to immune checkpoint inhibitors ci in early clinical trials ect

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Exploring the Immunogenicity of Noncanonical HLA-I Tumor Ligands Identified through Proteogenomics

Purpose: Tumor antigens are central to antitumor immunity. Recent evidence suggests that peptides from noncanonical (nonC) aberrantly translated proteins can be presented on HLA-I by tumor cells. Here, we investigated the immunogenicity of nonC tumor HLA-I ligands (nonC-TL) to better understand their contribution to cancer immunosurveillance and their therapeutic applicability. Experimental Design: Peptides presented on HLA-I were iden-tified in 9 patient-derived tumor cell lines from melanoma, gyneco-logic, and head and neck cancer through proteogenomics. A total of 507 candidate tumor antigens, including nonC-TL, neoantigens, cancer-germline, or melanocyte differentiation antigens, were tested for T-cell recognition of preexisting responses in patients with cancer. Donor peripheral blood lymphocytes (PBL) were in vitro sensitized against 170 selected nonC-TL to isolate antigen-specific T-cell recep-tors (TCR) and evaluate their therapeutic potential.Rudolf Virchow Center, Center for Integrative and Transla- tional Bioimaging, Julius-Maximilians-University Wueurorzburg, Wueurorzburg, German

Frequency and characteristics of familial melanoma in Spain: The FAM-GEM-1 Study

Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior

Low-dose irradiation for reversing immunotherapy resistance: how to translate?

The use of low-dose irradiation (LDI) for mobilizing innate and adaptive immunity is gaining interest among the scientific community. Recent evidence suggests that LDI can reprogramme the tumor microenvironment, induce inflammation and turn cold tumors susceptible to immunecheckpoint blockade therapy. Translating immuno-radiation preclinical findings in the clinic is more challenging than expected. We propose therapeutic strategies for combining LDI with immunotherapy, and emphasize the importance of pursuing clinical research to determine optimal radiation dosage, fractionation, volumes, and sequencing to stimulate immune-mediated tumor responses