Cyrille Cohen | Bar-Ilan University (original) (raw)

Papers by Cyrille Cohen

Immune checkpoint blockade (ICB) has shown unprecedented clinical success in treatment of cancer.... more Immune checkpoint blockade (ICB) has shown unprecedented clinical success in treatment of cancer. However, not all patients show adequate response, and the treatment can lead to a broad range of adverse effects. Therefore, early identification of potential responders to therapy, using non-invasive means, is a critical challenge for improving ICB. Herein, we engineered anti-Programmed Death Ligand 1 (aPDL1) nanoparticles with enhanced ICB immunotherapy efficacy. Using a mouse model for colon cancer, we show that the nanoparticles accumulated, penetrated and efficiently prevented tumor growth. Moreover, we found a direct correlation between the amount of nanoparticle accumulation within the tumor at 48 hours, as determined by CT, and the therapeutic response. This enabled subject stratification as potential responders or non-responders, at an early time point. Thus, by integrating prognostic and ICB-based therapeutic functions into one nanoparticle, we obtained a straightforward appro...

Journal for ImmunoTherapy of Cancer

ACS nano, Jan 20, 2017

Cancer immunotherapy has made enormous progress in offering safer and more effective treatments f... more Cancer immunotherapy has made enormous progress in offering safer and more effective treatments for the disease. Specifically, programmed death ligand 1 antibody (αPDL1), designed to perform immune checkpoint blockade (ICB), is now considered a pillar in cancer immunotherapy. However, due to the complexity and heterogeneity of tumors, as well as the diversity in patient response, ICB therapy only has a 30% success rate, at most; moreover, the efficacy of ICB can be evaluated only two months after start of treatment. Therefore, early identification of potential responders and nonresponders to therapy, using noninvasive means, is crucial for improving treatment decisions. Here, we report a straightforward approach for fast, image-guided prediction of therapeutic response to ICB. In a colon cancer mouse model, we demonstrate that the combination of computed tomography imaging and gold nanoparticles conjugated to αPDL1 allowed prediction of therapeutic response, as early as 48 h after t...

Journal for ImmunoTherapy of Cancer, 2016

Cancer immunology research, Aug 16, 2016

Immunotherapy treatment of patients with metastatic cancer has assumed a prominent role in the cl... more Immunotherapy treatment of patients with metastatic cancer has assumed a prominent role in the clinic. Durable complete response rates of 20-25% are achieved in patients with metastatic melanoma following adoptive cell transfer of T cells derived from metastatic lesions, responses that appear in some patients to be mediated by T cells that predominantly recognize mutated antigens. Here we provide a detailed analysis of the reactivity of T cells administered to a patient with metastatic melanoma who exhibited a complete response for over 3 years after treatment. Over 4,000 nonsynonymous somatic mutations were identified by whole-exome sequence analysis of the patient's autologous normal and tumor cell DNA. Autologous B cells transfected with 720 mutated minigenes corresponding to the most highly expressed tumor cell transcripts were then analyzed for their ability to stimulate the administered T cells. Autologous TIL recognized 10 distinct mutated gene products, but not the corre...

Molecular therapy : the journal of the American Society of Gene Therapy, Jun 5, 2016

Neoantigens unique to each patient's tumor can be recognized by autologous T cells through th... more Neoantigens unique to each patient's tumor can be recognized by autologous T cells through their T-cell receptor (TCR) but the low frequency and/or terminal differentiation of mutation-specific T cells in tumors can limit their utility as adoptive T-cell therapies. Transfer of TCR genes into younger T cells from peripheral blood with a high proliferative potential could obviate this problem. We generated a rapid, cost-effective strategy to genetically engineer cancer patient T cells with TCRs using the clinical Sleeping Beauty transposon/transposase system. Patient-specific TCRs reactive against HLA-A*0201-restriced neoantigens AHNAK(S2580F) or ERBB2(H473Y) or the HLA-DQB*0601-restricted neoantigen ERBB2IP(E805G) were assembled with murine constant chains and cloned into Sleeping Beauty transposons. Patient peripheral blood lymphocytes (PBL) were co-electroporated with SB11 transposase and Sleeping Beauty transposon, and transposed T cells were enriched by sorting on murine TCRβ...

Methods in molecular biology (Clifton, N.J.), Jan 20, 2016

Melanoma tumors are known to harbor a high number of mutations leading to the expression of neo-a... more Melanoma tumors are known to harbor a high number of mutations leading to the expression of neo-antigens which can be recognized by the patient adaptive immune system. In this regard, immunotherapies involving adoptive cell transfer (ACT) of tumor-specific T-cells constitute a promising approach to treat melanoma. However, these cells do not always preexist in the patient or are difficult to isolate and/or expand. Thus, as the specificity of T-lymphocytes is determined by their T-cell receptor (TCR), it is possible to convert peripheral T-cells into cancer specific lymphocytes by transducing them to express a receptor that recognizes a defined tumor epitope. To this end, retroviral vectors can be used to efficiently transduce actively dividing cells such as proliferating T cells, while being relatively safe to the user. As we show herein, this approach is powerful and can be easily implemented, paving the way to the development of advanced research tools and potent clinical immunoth...

Cancer Immunol Immunother, 2010

Journal for ImmunoTherapy of Cancer, 2015