Selective activation of interleukin-2/interleukin-15 receptor signaling in tumor microenvironment using paired bispecific antibodies

Background
Owing to their roles in promoting T cell and natural killer (NK) cell activation and proliferation, interleukins-2 (IL-2) and interleukins-15 (IL-15) have been pursued as promising pathways to target in cancer immunotherapy. Nonetheless, th…

Leucine-rich {alpha}-2 glycoprotein 1 (LRG1) during inflammatory complications after allogeneic stem cell transplantation and CAR-T cell therapy

Background
Previous data indicated that the leucine-rich α-2 glycoprotein 1 (LRG1) pathway contributes to vascular dysfunction during cancer growth. Therapeutic targeting of LRG1 normalized tumor vessel dysfunction and enhanced the efficacy of a…

Optimization of Adcitmer, a Monomethyl-Auristatin E bearing antibody-drug conjugate for the treatment of CD56-expressing cancers

The cell adhesion protein CD56 has been identified as a potential therapeutic target in several solid tumors and hematological malignancies. Recently, we developed a CD56-directed antibody-drug conjugate (ADC), called Adcitmer and demonstrated its ant…

Potent and durable control of mesothelin-expressing tumors by a novel T cell-secreted bi-specific engager

Background
The glycosylphosphatidylinositol-anchored cell surface protein mesothelin (MSLN) shows elevated expression in many malignancies and is an established clinical-stage target for antibody-directed therapeutic strategies. Of these, the harnessi…

Boosting tumor homing of endogenous natural killer cells via therapeutic secretomes of chemically primed natural killer cells

Background
Natural killer (NK) cells play a critical role in modulating immune responses by secreting soluble factors, including chemotactic cytokines. Our previous study demonstrated the potent antitumor activity of Chem_NK, referring to NK cells che…

Tumor-specific CD8+ T cells from the bone marrow resist exhaustion and exhibit increased persistence in tumor-bearing hosts as compared with tumor-infiltrating lymphocytes

Background
Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor-infiltrat…

Phosphatidylserine as a tumor target for CAR-T cell therapy

Background
Phosphatidylserine (PS) exposed on apoptotic cells promotes immune clearance of dead cells without inducing inflammation. Conversely, PS exposure on live tumor cells promotes an immunosuppressive tumor microenvironment that hinders antitumo…

Pooled screening for CAR function identifies novel IL-13R{alpha}2-targeted CARs for treatment of glioblastoma

Background
Chimeric antigen receptor (CAR) therapies have demonstrated potent efficacy in treating B-cell malignancies, but have yet to meaningfully translate to solid tumors. Nonetheless, they are of particular interest for the treatment of glioblast…

CD4 T cell depletion increases memory differentiation of endogenous and CAR T cells and enhances the efficacy of Super2 and IL-33-armored CAR T cells against solid tumors

Background
Responsiveness to chimeric antigen receptor (CAR) T cell therapy correlates with CAR T cell expansion and persistence in vivo. Multiple strategies improve persistence by increasing stem-like properties or sustaining CAR T cell activity with…

Real-world outcomes with tisagenlecleucel in aggressive B-cell lymphoma: subgroup analyses from the CIBMTR registry

Background
Tisagenlecleucel, a CD19 chimeric antigen receptor T-cell therapy, is approved for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL) after ≥2 lines of therapy. When used …

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