A polemic in response to Freiwan et al is given.In this issue of Blood, Freiwan et al demonstrate the feasibility of using selected, naturally occurring CD^CD7-T cells to generate ^CD7- targeting chimeric antigen receptor (CAR) T cells without ^CD7- directed fratricide and show that CAR^CD7-T cells have favorable biol. characteristics.The potential of exploiting CD7- T cells can facilitate the manufacturing of CD7 CAR T cells for T-cell acute lymphoblastic leukemia (T-ALL).In addition, the authors report that beyond T-ALL targeting, CD19-specific CAR^CD7-T cells show improved immunotherapeutic properties leading to better antitumor function, and thus, CD7-T cells are an interesting effector population for CAR Tcell therapy of hematol. malignancies.

01 Nov 2022·Clinical Lymphoma Myeloma and Leukemia

Patterns of Utilization and Outcomes of Autologous Stem Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements

Article

Author: Narkhede, Mayur ; Mehta, Amitkumar ; Bal, Susan ; Bliven, Sean Patrick ; Shea, Lauren ; Goyal, Gaurav

BACKGROUNDPatients with Diffuse Large Bcell Lymphoma (DLBCL) with MYC and BCL2 and/or BCL6 gene rearrangements [double-hit lymphoma/triple-hit lymphoma (DHL/THL)] have poor prognosis in the relapsed/refractory setting.METHODSWe utilized a real-world deidentified database of DLBCL patients and report patterns of therapy utilization in relapsed/refractory DLBCL. We used log-rank test to compare real-world overall survival (rwOS) among DHL and non-DHL subgroups for CAR Tcell therapy or ASCT respectively, stratified for prior lines of therapy.RESULTSOf all 7,877 patients with DLBCL, 367 patients had DHL while 6113 had non-DHL. Second line chemotherapy was administered to 147 DHL patients and 1517 non-DHL. 1393 were excluded, including 934 with unknown DHL/THL status. Approximately 47% received salvage intent chemotherapy in the DHL subgroup, of which 19% patients eventually received ASCT, while 34% received salvage intent chemotherapy in the non-DHL/THL group with 32% receiving ASCT. DHL/THL status negatively influenced median rwOS for patients who underwent ASCT in the second-line while it was associated with numerically inferior but without statistically significant rwOS among patients that underwent CAR Tcell therapy on multivariable analysis.CONCLUSIONrwOS of relapsed DHL/THL is inferior to non-DHL/THL. Fewer patients with DHL/THL were able to proceed with ASCT after salvage chemotherapy compared to non-DHL/THL. ASCT as second-line therapy for relapsed DHL/THL had worse rwOS than for non-DHL/THL, consistent with the natural history of DHL/THL. This difference was not seen for CAR Tcell therapy, which combined with promising results from clinical trials, suggests a greater role for CAR T-cell therapy in relapsed/refractory DHL.

01 Aug 2022·Current Gene TherapyQ4 · MEDICINE

CAR-NK Cells for Cancer Therapy: Molecular Redesign of the Innate Antineoplastic Response

Q4 · MEDICINE

Review

Author: Cienfuegos-Jimenez, Oscar ; Rojas-Martinez, Augusto ; Vazquez-Garza, Eduardo

:The Chimeric Antigen Receptor (CAR) has arisen as a powerful synthetic biology-based technology with demonstrated versatility for implementation in T and NK cells. Despite CAR T cell successes in clinical trials, several challenges remain to be addressed regarding adverse events and long-term efficacy. NK cells present an attractive alternative with intrinsic advantages over T cells for treating solid and liquid tumors. Early preclinical and clinical trials suggest at least two major advantages: improved safety and an off-the-shelf application in patients due to its HLA independence. Due to the early stages of CAR NK translation to clinical trials, limited data is currently available. By analyzing these results, it seems that CAR NK cells could offer a reduced probability of Cytokine Release Syndrome (CRS) or Graft versus Host Disease (GvHD) in cancer patients, reducing safety concerns. Furthermore, NK cell therapy approaches may be boosted by combining it with immunological checkpoint inhibitors and by implementing genetic circuits to direct CAR-bearing cell behavior. This review provides a description of the CAR technology for modifying NK cells and the translation from preclinical studies to early clinical trials in this new field of immunotherapy.

100 Deals associated with Anti-CD22 CAR-T cell therapy (Kecellitics Biotech)

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Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Preclinical	CN	Beijing Kecellitics Biotech Co., Ltd.	-

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