Oncogenic MYD88 mutations in lymphoma: novel insights and therapeutic possibilities

AbstractOncogenicMYD88 mutations, most notably the Leu 265 Pro (L265P) mutation, were recently identified as potential driver mutations in various B-cell non-Hodgkin Lymphomas (NHLs). The L265P mutation is now thought to be common to virtually all NHLs and occurs in between 4 and 90% of cases, depending on the entity. Since it is tumor-specific, the mutation, and the pathways it regulates, might serve as advantageous therapeutic targets for both conventional chemotherapeutic intervention, as well as immunotherapeutic strategies. Here, we review recent progress on elucidating the molecular and cellular processes affected by the  L265P mutation ofMYD88, describe a new in vivo model for MyD88 L265P-mediated oncogenesis, and summarize how these findings could be exploited therapeutically by specific targeting of signaling pathways. In addition, we summarize current and explore future possibilities for conceivable immunotherapeutic approaches, such as L265P-derived peptide vaccination, adoptive transfer of L265P-restricted T cells, and use of T-cell receptor-engineered T cells. With clinical trials regarding their efficacy rapidly expanding to NHLs, we also discuss potential combinations of immune checkpoint inhibitors with the described targeted chemotherapies of L265P signaling networks, and/or with the above immunological approaches as potential ways of targetingMYD88-mutated lymphomas in the future.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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In conclusion, our data demonstrate that IFN-DC-based vaccination plus lenalidomide exert an additive therapeutic effect in xenochimeric mice bearing established lymphoma. These results may pave the way to evaluate this co mbination in the clinical ground.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Cancer immunotherapies have primarily focused on generating tumoricidal CD8 T cells. However, recent data demonstrate a critical role for CD4 T cells in tumor immunity. CD4 T cells against epitopes derived from mutated tumor-associated neo-antigens (neoAg) conferred protection against tumor growth in animal models of neoAg vaccine therapy. In clinical studies, immunity elicited by neoAg vaccines was associated with improved survival, even though the majority of immune responses were CD4 T cells that did not have cytolytic activity.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Patients with mesothelioma are now eligible for a multicancer clinical trial studying the effectiveness of personalized immunotherapy at the University of California, San Diego Medical Center. The phase I clinical trial involves a combination of Keytruda (pembrolizumab), a proven immunotherapy drug, and an individualized vaccine based upon the genetic mutations found in each patient’s cancer. “This is the future of cancer treatment,” Dr. Ezra Cohen, principal investigator and director of the San Diego Center for Precision Immunotherapy, told The Mesothelioma Center at Asbestos.com. “Now, we still ha...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Despite efficient suppression of plasma viremia in people living with HIV (PLWH) on cART, evidence of HIV-induced immunosuppression remains, and normally benign and opportunistic pathogens become major sources of co-morbidities, including virus-induced cancers. In fact, cancer remains a primary cause of death even in virally suppressed PLWH. Natural killer (NK) cells provide rapid early responses to HIV infection, contribute substantially to disease modulation and vaccine protection, and are also major therapeutic targets for cancer immunotherapy. However, much like other lymphocyte populations, recent burgeoning evidence ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, the potential of intratumoral immune modulation with poly (I:C), Resiquimod (R848) and CCL20 (MIP3α) was explored. Biodegradable polymeric nanoparticles were used as delivery vehicles for slow and sustained release of these drugs in the tumor area and were combined with specific immunotherapy based on therapeutic peptide vaccination in two aggressive murine carcinoma and lymphoma tumor models. Whereas nanoparticle delivery of poly (I:C) or R848 improved therapeutic efficacy, the combination with MIP3α remarkably potentiated the cancer vaccine antitumor effects. The long-term survival increased to...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research
This article introduces the main concepts and addresses the most relevant clinical modalities of cellular immunotherapies for hematological malignancies: antigen non-specific T cell therapy, genetically modified T cell receptor (TCR) T cell therapy, chimeric antigen receptor (CAR) T cell therapy, and CAR-T cell clinical trials in leukemia, lymphoma, and multiple myeloma. Clinical trials have shown encouraging results, but future studies may need to incorporate novel CAR constructs or targets with enhanced safety and efficacy to ensure long-term benefits. PMID: 31338822 [PubMed - in process]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
This review focuses on what is the biological basis of esophageal cancer for immunotherapy, how to screen out the patients who can benefit from immunotherapy, and whether the toxic side effects of immunotherapy are manageable. AbstractConsidering the benefits of immunotherapy in advanced melanoma, non –small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma, we begin to consider whether immunotherapy is effective for esophageal cancer, which is extremely malignant and has a poor prognosis. There are a large number of clinical trials to study the applicatio n of immunotherapy suc...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: REVIEW Source Type: research
AbstractBackgroundPet dogs spontaneously develop lymphoma. An anthracycline-based multidrug chemotherapy regimen represents the treatment cornerstone; however, cure is rarely achieved. We have been treating dogs with B-cell lymphoma with an autologous vaccine (APAVAC ®) and CHOP-based chemotherapy since 2011.MethodsTo better characterize the safety and efficacy of APAVAC ®, and to find the best candidates for immunotherapy, we designed a retrospective study on all dogs treated with chemo-immunotherapy to date and compared them with those dogs treated with chemotherapy only. All dogs were completely staged and re-st...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Marjolein Schluck1,2, Roel Hammink1,2, Carl G. Figdor1,2,3, Martijn Verdoes1,3*† and Jorieke Weiden1,2,3*† 1Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands 2Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, Nijmegen, Netherlands 3Institute for Chemical Immunology, Nijmegen, Netherlands Traditional tumor vaccination approaches mostly focus on activating dendritic cells (DCs) by providing them with a source of tumor antigens and/or adjuvants, which in turn activate tumor-reactive T c...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Hui Zhou, Xiaoyan Fu, Qian Li and Ting Niu* Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clin...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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