PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

A Tender Reduced-Intensity Conditioning for the Unfit: A Novel 4 Gy Total Body Irradiation-Based Conditioning Followed by Two-Step Haploidentical Stem Cell Transplant, Results of a Prospective Trial.

Allogeneic hematopoietic stem cell transplant (HSCT) remains the only potentially curative treatment for many hematologic malignancies (HM). We previously developed a two-step approach that separates the lymphoid and myeloid portions of the graft, allowing a consistent T cell dosing and sparing the stem cells from the effect of post-transplant cyclophosphamide (CY). The two-step approach demonstrated safety and efficacy in patients treated with myeloablative and reduced-intensity conditioning.

Safety and feasibility of third-party cytotoxic T lymphocytes for high-risk patients with COVID-19.

Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment.

A prospective study of posttransplant cyclophosphamide for unrelated donor peripheral blood stem cell transplant with special attention to graft content and the impact of a higher γδ T cell dose.

Posttransplant cyclophosphamide (PtCy) has been shown to decrease post-hematopoietic stem cell transplant acute and chronic graft-versus-host disease (GVHD). In this study, PtCy was used in 44 patients along with mycophenolate and tacrolimus with HLA matched (29) and mismatched (15) unrelated donors to determine the impact of graft content on outcome; thus, all patients had flow cytometric analysis of their graft content including the number of B cells, NK cells, and various T cell subsets. Higher γδ T cell dose was associated with the development of acute GVHD (p = .

Chimeric Antigen Receptor T-Cell Access in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Association of Access with Social Determinants of Health and Travel Time to Treatment Centers.

Large B-cell lymphoma (LBCL) is the most common type of non-Hodgkin lymphoma. Chimeric antigen receptor T-cell (CAR T) therapy represents a novel treatment with curative potential for relapsed or refractory (R/R) LBCL, but there are access barriers to this innovative therapy that are not well-studied. Study objectives were: (1) Assess the impact of geographic factors and social determinants of health (SDOH) on access to treatment with CAR T in a sample of patients with R/R LBCL and ≥2 prior lines of therapy (LOT).

Chimeric Antigen Receptor T - Cell Therapy for Large B-Cell Lymphoma Patients with Central Nervous System Involvement, a Systematic Review and Meta-analysis.

Chimeric Antigen Receptor T-cell (CAR T-cell) therapy is an effective treatment for relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, patients with central nervous system (CNS) lymphoma were excluded in most of the CAR T-cell therapy trials. This meta-analysis assesses the efficacy with CAR T-cell therapy in LBCL patients with CNS involvement.

Donor-Derived Malignancy and Transplantation Morbidity: Risks of Patient and Donor Genetics in Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a key treatment option for hematologic malignancies (HMs), although it carries significant risks. Up to 30% of patients relapse after allo-HSCT, of which up to 2% to 5% are donor-derived malignancies (DDMs). DDMs can arise from a germline genetic predisposition allele or clonal hematopoiesis (CH) in the donor.

The two-step approach to allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) provides the only potentially curative option for multiple hematological conditions. However, allogeneic HSCT outcomes rely on an optimal balance of effective immune recovery, minimal graft-versus-host disease (GVHD), and lasting control of disease. The quest to attain this balance has proven challenging over the past few decades.

Chimeric antigen receptor T-cell treatment patterns in relapsed or refractory large B-cell lymphoma.

To investigate real-world chimeric antigen receptor (CAR) T-cell therapy treatment patterns. Relapsed/refractory large B-cell lymphoma patients who received CAR T-cell therapy were identified. Patient characteristics, setting of CAR T-cell infusion, incidence of CAR T-cell therapy-associated adverse events and healthcare resource utilization were assessed.

Expert consensus on microtransplant for acute myeloid leukemia in elderly patients -report from the international microtransplant interest group.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4).

Endemic or regionally limited bacterial and viral infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review.

Literature discussing endemic and regionally limited infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America is scarce. This Worldwide Network for Blood and Marrow Transplantation (WBMT) article is part one of two papers aiming to provide guidance to transplantation centres around the globe regarding infection prevention and treatment, and considerations for transplantation based on current evidence and expert opinion. These recommendations were initially formulated by a core writing team from the WBMT and subsequently underwent multiple revisions by infectious disease experts and HSCT experts.

Allogeneic Chimeric Antigen Receptor T Cells for Hematologic Malignancies.

Autologous chimeric antigen receptor (CAR) T cell therapy has been extensively studied over the past decades. Currently, autologous CAR T products are FDA-approved to treat B cell acute lymphoblastic leukemia (B-ALL), large B cell, mantle cell, and follicular lymphomas, and multiple myeloma. However, this therapy has drawbacks including higher cost, production lead time, logistical complexity, and higher risk of manufacturing failure.

Chimeric Antigen Receptor T Cell Therapy For Solid Tumors.

Chimeric antigen receptor T (CAR T) cell therapy has revolutionized the management of lymphoid malignancies. However, it is still in its early phase and is facing many obstacles in solid tumors. Therapeutic challenges in solid tumor lead to tumor target diversification and drive new innovations for the improvement of clinical efficacy.

Chimeric Antigen Receptor T-cell Therapy for Acute Myeloid Leukemia.

Chimeric antigen receptor (CAR) T-cells targeting CD19 have drastically improved the outcomes of B-cell malignancies; however, the success has not yet extended to myeloid malignancies such as acute myeloid leukemia (AML). Main impediments in the development of CAR T therapy in AML include difficulty in identifying appropriate target antigens that are specific to myeloid leukemia stem cells while sparing the healthy hematopoietic stem progenitor cells (HSPCs). Herein, we discuss the current state of CAR T-cell therapy in AML, highlighting recent progress and limitations in clinical translation.

Chimeric Antigen Receptor T-cell Therapies in Lymphoma Patients with Central Nervous System Involvement.

Background And Objective: CAR T-cell therapy has significantly improved the outcomes of patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). However, most clinical trials excluded patients with central nervous system (CNS) involvement due to uncertain efficacy and safety.

Material And Methods: On January 1, 2022, we searched PubMed to identify all published literature associated with current commercial CAR T-cell therapies for B-NHL, including tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), and lisocabtagene maraleucel (liso-cel).

Next-Generation Chimeric Antigen Receptor T-cells.

The U.S. Food and Drug Administration (FDA) approved 6 CAR T cell (CAR-T) products, including tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), lisocabtagene maraleucel (liso-cel), idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel) in the last 5 years.