MSLN CAR-T / National Cancer Institute - LARVOL DELTA

The Next Generation “off-the-shelf” Universal CAR for Adoptive Immunotherapy (SITC 2019) - P1; "Background: Adoptive immunotherapy using autologous T cells redirected with chimeric antigen receptors (CARs) has emerged as a powerful means of treating cancer, such as B-cell malignancy... Therefore, we believe this next generation Tscm-enriched universal CAR T cells employing the same BCMA vector will provide another alternative choice for multiple myeloma patients in an "off-the-shelf" manner similar to other biological drugs."

Immunotherapy perspectives in the new era of B-cell editing. (PubMed, Blood Adv) - "Its most recent and successful weapons are autologous T cells carrying chimeric antigen receptors, engineered purposely for binding cancer-specific antigens and therefore used for so-called adoptive immunotherapy...This unique affiliation will soon and considerably expand the scope of diseases susceptible to adoptive immunotherapy and of immune cells available for being reshaped as therapeutic tools, including B cells. Following the monumental success story of passive immunotherapy with monoclonal antibodies (mAbs), we are thus entering into a new era, where a combination of gene therapy/cell therapy will enable reprogramming of the patient's immune system and notably endow his B cells with the ability to produce therapeutic mAbs on their own."

Journal • Gene Therapies • Oncology

MR1-restricted T cells: the new dawn of cancer immunotherapy. (PubMed, Biosci Rep) - "The adoptive transfer of engineered autologous T cells, such as chimeric antigen receptor (CAR) T cells, has been remarkably successful in patients with leukemia and lymphoma with cluster of differentiation (CD)19 expression...These studies provide additional information on MR1-T cells for cancer immunotherapy. This review describes the complexity of MR1-T cell TCR in diseases and the future of cancer immunotherapy."

IO Biomarker • Journal • Hematological Malignancies • Leukemia • Lymphoma • Oncology

[VIRTUAL] Cord-blood derived NK cells, and CAR-T cells, an attractive improved immunotherapy treatment to be considered for hematological malignancies (SITC 2020) - "Administration of autologous T cells modified with a chimeric antigen receptor (CAR) against B cell maturation antigen (BCMA) has achieved high percentages of complete responses. Unfortunately, the lack of persistence of CART-BCMA cells in the patient leads to relapses...Finally, an in vivo model of advanced MM with consecutive challenge to MM cells evidenced that the addition of CB-NK achieved the highest efficacy of the treatment. Conclusions Our results suggest that the addition of ‘off-the-shelf’ CB-NK to CART cells leads to a faster and earlier immune response of CART cells with higher long-term maintenance of the anti-tumor response, suggesting this combinatorial therapy as an attractive immunotherapy option for MM patients."

CAR T-Cell Therapy • IO Biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • IFNG • TNFA

[VIRTUAL] Cord-blood derived NK cells, and CAR-T cells, an attractive improved immunotherapy treatment to be considered for hematological malignancies (SITC 2020) - "Administration of autologous T cells modified with a chimeric antigen receptor (CAR) against B cell maturation antigen (BCMA) has achieved high percentages of complete responses. Unfortunately, the lack of persistence of CART-BCMA cells in the patient leads to relapses...Finally, an in vivo model of advanced MM with consecutive challenge to MM cells evidenced that the addition of CB-NK achieved the highest efficacy of the treatment. Conclusions Our results suggest that the addition of ‘off-the-shelf’ CB-NK to CART cells leads to a faster and earlier immune response of CART cells with higher long-term maintenance of the anti-tumor response, suggesting this combinatorial therapy as an attractive immunotherapy option for MM patients."

CAR T-Cell Therapy • IO Biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • IFNG • TNFA

Adoptive cell therapy using engineered natural killer cells. (PubMed, Bone Marrow Transplant) - "The generation of autologous T cells expressing a chimeric antigen receptor (CAR) have revolutionized the field of adoptive cellular therapy...The availability of NK cells from multiple sources and their proven safety profile in the allogeneic setting positions them as attractive contenders for cancer immunotherapy. In this review, we discuss advantages and potential drawbacks of using NK cells as a novel cellular therapy against hematologic malignancies, as well as strategies to further enhance their effector function."

Journal • Review • Hematological Malignancies • Oncology

Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors. (clinicaltrials.gov) - P1; N=10; Recruiting; Sponsor: Chinese PLA General Hospital; Trial completion date: Jun 2020 ➔ Dec 2020; Trial primary completion date: Dec 2019 ➔ Oct 2020

Clinical • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • MSLN

Selectivity and specificity of engineered T cells expressing KITE-585, a chimeric antigen receptor targeting B-cell maturation antigen (BCMA) (AACR 2017) - "One such technique is to use adoptive transfer of engineered autologous T cells expressing a chimeric antigen receptor (CAR) directed against a tumor antigen. These studies highlight the tractability of this cell microarray approach for determining the specificity of novel CAR constructs expressed in T cell. Demonstrating the selectivity and specificity of anti-BMCA CAR T cells further supports the progression of KITE-585 towards Phase 1 clinical studies in MM patients."

CAR T-Cell Therapy • Biosimilar • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Development of KITE-585: A fully human BCMA CAR T-cell therapy for the treatment of multiple myeloma (AACR 2017) - "One such approach is to use adoptive transfer of engineered autologous T cells expressing a chimeric antigen receptor (CAR) directed against malignant cells. The results of these studies highlight the potential of targeting BCMA with adoptive transfer of engineered T cells for the treatment of MM. Given these positive findings, progress towards Phase 1 clinical studies in MM patients with KITE-585 is continuing."

CAR T-Cell Therapy • Biosimilar • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

CAR T Cell Receptor Immunotherapy Targeting Mesothelin for Patients With Metastatic Cancer (clinicaltrials.gov) - P1/2; N=136; Recruiting; Sponsor: National Cancer Institute (NCI); Suspended ➔ Recruiting; N=15 ➔ 136

Enrollment change • Enrollment open • Biosimilar • Gastrointestinal Cancer • Immunology • Mesothelioma • Oncology • Ovarian Cancer • Pancreatic Cancer

Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors. (clinicaltrials.gov) - P1; N=10; Recruiting; Sponsor: Chinese PLA General Hospital; Trial completion date: Jun 2019 ➔ Jun 2020; Trial primary completion date: Dec 2018 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date • MSLN

FT819: Translation of Off-the-Shelf TCR-Less Trac-1XX CAR-T Cells in Support of First-of-Kind Phase I Clinical Trial (ASH 2019) - "Long-term follow-up of adoptive transfer of autologous T cells expressing a chimeric antigen receptor (CAR) directed to CD19 antigen has demonstrated encouraging, durable clinical outcome in various B cell malignancies. Small molecules are known to modulate cell functions and when treated with compound A, FT819-iTs further delayed tumor growth and increased anti-tumor potency when compared to DMSO treated group (Day 17, P<0.05). Collectively, the preclinical studies suggest that FT819 is a consistent and uniform off-the-shelf CAR T cell product candidate with the first-of-kind Phase 1 clinical trial for the treatment of B cell malignancies in an allogeneic setting study planned for 2020."

CAR T-Cell Therapy • Clinical • IO Biomarker • P1 data • CD27 • CD8

Foamy Virus Based Vectors for CAR-T Cell Development (ASH 2019) - "Introduction A novel approach that can cover the therapeutic gap in NHL treatment are the autologous T cells, expressing Chimeric Antigen Receptors (CAR-T cells) against tumor markers...FV CARTs derived from PB of CLL patients were capable of mediating comparable cytotoxicity levels as their LV-derived counterparts. Overall, we provide a proof of concept that FVs could be a safe and efficient alternative to LV derived vectors for CAR-T cells."

CAR T-Cell Therapy • IO Biomarker • CD8 • IFNG

Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. (PubMed, JCI Insight) - P1; "CTL019 may improve duration of response to standard multiple myeloma therapies by targeting and precipitating secondary immune responses against myeloma-propagating cells."

CAR T-Cell Therapy • Journal

MDS AS A CAUSE FOR PROLONGED HEMATOLOGIC TOXICITY AFTER TREATMENT WITH CD19 TARGETED CAR‐T CELL THERAPY IN PATIENTS WITH RELAPSED REFRACTORY LYMPHOMA (ICML 2019) - "Introduction: The advent of adoptive cellular therapy utilizing autologous T cells expressing chimeric antigen receptors (CAR-T) against CD19 has revolutionized relapsed and refractory B cell lymphoma treatment...Two patients developed severe CRS requiring tocilizumab and corticosteroids... Median age was 74 (range: 57-76). Two patients had GCB type, 2 had non-GCB type DLBCL. The median number of lines of therapy prior to CAR-T cell therapy was 5."

CAR T-Cell Therapy • Clinical

Development and Validation of In-House CAR-T Cell Manufacturing (ASGCT 2019) - "Treatment of patients with autologous T cells expressing chimeric antigen receptor (CAR-T) is a promising adoptive cell therapy already FDA approved for the treatment of hematologic malignancies...The result is patients waiting for a lifesaving treatment until there is a slot open to manufacture their product. Our goal is to eliminate the need for external manufacturing by making products in-house, resulting in a cheaper and more flexible process for generating CAR- T products and a shorter time from target discovery to patient delivery."

CAR T-Cell Therapy

Sensitive detection and quantification of CAR-T cells in the treated patients (AACR 2019) - "...In particular, autologous T cells modified with a chimeric antigen receptor (CAR-T) has recently been regulatory-approved for the treatment of the patients of CD19+ acute B-cell leukemia [1][2]...Our method detection, monitoring and characterization of CAR-T offers an great opportunity in the clinical setting to monitor patient treatment and to understand the treatment mechanisms, that otherwise is unavailable. This could become an useful diagnostics to provide guidance on the treatment and prognosis of patients."

CAR T-Cell Therapy • Clinical

Generation of novel single cell-derived engineered master pluripotent cell line as a renewable source for off-the-shelf TCR-less CAR T cells in support of first-of-kind clinical trial (AACR 2019) - "Adoptive transfer of autologous T cells expressing chimeric antigen receptor (CAR) has shown great promise in the treatment of blood malignancies. Validated, TRAC-targeted hiPSC clones were cryopreserved (~150 vials per clone) and are currently being assessed for off-target editing, differentiation propensity into highly-functional T cells, genomic stability, clone identity, sterility and lack of mycoplasma detection. In summary, using our novel iPSC technology platform for reprogramming, single cell engineering and multiplex high-throughput screening of hiPSCs, we have generated clinical-grade clonal master hiPSC lines in support of our first-of-kind clinical trials evaluating FT819 allogenic off-the-shelf hiPSC-derived TCR-less TRAC-CAR19 T cells for the treatment of blood malignancies."

CAR T-Cell Therapy • IO Biomarker • Late-breaking abstract

Study of Anti-Mesothelin Car NK Cells in Epithelial Ovarian Cancer (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: Allife Medical Science and Technology Co., Ltd.; Initiation date: Nov 2018 ➔ Mar 2019

Clinical • Trial initiation date