Targeting Cancer Associated Fibroblasts in the Bone Marrow Prevents Resistance to Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma

Cellular immunotherapy is a rapidly progressing field in multiple myeloma (MM). Multiple clinical trials have reported impressive efficacy of B cell maturation antigen (BCMA) directed chimeric antigen receptor cell therapy (BCMA CART) in MM. While trials demonstrated a high response rate, the durable response rate is around 30%. Most patients lose their CART cells, and the disease relapses within the first year, suggesting an inhibition by the MM tumor microenvironment (TME). Therefore strategies to overcome this inhibition would represent a major advance in this field.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 333 Source Type: research

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Chimeric antigen receptor (CAR) T cell immunotherapy has been a major advancement in cancer therapeutics. Reprogramming of T cells is achieved by using gammaretroviral or lentiviral vectors, which may interfere with human immunodeficiency virus type 1 (HIV-1) nucleic acid amplification testing (NAAT). Here, we describe three clinical scenarios in which CAR T cell immunotherapy interfered with HIV-1 testing, including (i) routine infectious disease screening prior to stem cell transplantation in a 16-year-old female with B cell acute lymphoblastic leukemia, post CAR T cell treatment; (ii) routine infectious disease screenin...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Virology Source Type: research
Inokuchi Despite therapeutic advances over the past decades, multiple myeloma (MM) remains a largely incurable disease with poor prognosis in high-risk patients, and thus new treatment strategies are needed to achieve treatment breakthroughs. MM represents various forms of impaired immune surveillance characterized by not only disrupted antibody production but also immune dysfunction of T, natural killer cells, and dendritic cells, although immunotherapeutic interventions such as allogeneic stem-cell transplantation and dendritic cell-based tumor vaccines were reported to prolong survival in limited populations of MM p...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Chimeric antigen receptor (CAR)-T cell therapy is a new and powerful class of cancer immunotherapy [1,2]. Clinical trials of CAR-T cell therapy targeting the B cell marker CD19 have shown promising results for the treatment of hematologic malignancies, including acute lymphoblastic leukemia (ALL) [3-7], chronic lymphocytic leukemia [8,9], and non-Hodgkin lymphoma (NHL) [10,11]. CAR-T cell therapy targeting B cell maturation antigen (BCMA) has also been demonstrated to be effective for treating multiple myeloma (MM) [12-15].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Chimeric antigen receptor (CAR)-T cell therapy is a new and powerful class of cancer immunotherapy [1,2]. Clinical trials of CAR-T cell therapy targeting the B-cell marker CD19 have shown promising results for the treatment of hematologic malignancies, including acute lymphoblastic leukemia (ALL) [3 –7], chronic lymphocytic leukemia (CLL) [8,9], and non-Hodgkin lymphoma (NHL) [10,11]. CAR-T cell therapy targeting B-cell maturation antigen (BCMA) has also been demonstrated to be effective for treating multiple myeloma (MM) [12–15].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
ConclusionsThese data demonstrate that a transplantation protocol involving only selective tumor-reactive donor T cell families is an effective immunotherapy and results in long-term survival in a mouse model of human MM. The results highlight the need to develop similar ATCT strategies for MM patients that result in enhanced survival without symptoms of GvHD.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
We describe three clinical scenarios in which CAR T- cell immunotherapy interfered with HIV-1 testing including: (1) routine infectious disease screening prior to stem cell transplantation in a 16-year-old female with B-cell acute lymphoblastic leukemia, status post CAR T- cell treatment (2) routine infectious disease screening prior to 2nd CAR T- cell collection in a 65-year-old male with diffuse large B-cell lymphoma who failed initial CAR T- cell treatment and (3) routine infectious risk assessment following an occupational health exposure from a 58 -year-old male with multiple myeloma, status post CAR T- cell treatment...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: J Clin Microbiol Source Type: research
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In some patients with multiple myeloma (MM), the original M protein disappears and one or multiple smaller immunoglobulins, called oligoclonal bands (OCB), emerge following autologous stem cell transplant (ASCT). OCB are associated with improved disease-free survival (DFS) and may be associated with early immune system recovery. Patients in phase I/II clinical trials at the University of Maryland Greenebaum Cancer Center who received anti CD3-CD28 co-stimulated and engineered autologous T cells shortly after ASCT had early, rapid, and robust T cell recovery.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the immune system for the entire life span of the mouse. Even if this class of treatment is not actually permanent in the same way in humans, and merely long-lasting, it still seems a promising step towards enhancing the immune system at any age, not just trying to repair it when it fails in later life. They've been called the "special forces" of the immune system: invariant natural killer T cells. Alth...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
CCR Grand Rounds James Kochenderfer, M.D., is a tenure-track investigator in the Experimental Transplantation and Immunology Branch (ETIB) of the National Cancer Institute (NCI). For the past 12 years, Dr. Kochenderfer has focused on a full range of chimeric antigen receptor (CAR) research from designing and cons tructing new CARs to conducting clinical trials. Dr. Kochenderfer designed and constructed a novel anti-CD19 CAR and then participated in a clinical trial of this CAR. This clinical trial was the first to demonstrate antigen-specific activity of anti-CD19 CARs in humans. This work in anti-CD19 CAR T cells led to...
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video
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