Strategies for Improving CAR T Cell Persistence in Solid Tumors.

CAR T cells require optimization to be effective in patients with solid tumors. There are many barriers affecting their ability to succeed. One barrier is persistence, as to achieve an optimal antitumor response, infused CAR T cells must engraft and persist.

Distinct host preconditioning regimens differentially impact the antitumor potency of adoptively transferred Th17 cells.

Background: How distinct methods of host preconditioning impact the efficacy of adoptively transferred antitumor T helper cells is unknown.

Methods: CD4 T cells with a transgenic T-cell receptor that recognize tyrosinase-related peptide (TRP)-1 melanoma antigen were polarized to the T helper 17 (Th17) phenotype and then transferred into melanoma-bearing mice preconditioned with either total body irradiation or chemotherapy.

Results: We found that preconditioning mice with a non-myeloablative dose of total body irradiation (TBI of 5 Gy) was more effective than using an equivalently dosed non-myeloablative chemotherapy (cyclophosphamide (CTX) of 200 mg/kg) at augmenting therapeutic activity of antitumor TRP-1 Th17 cells.

IL15 and IL21: Better When Membrane-Tethered Together on Antitumor T Cells.

Systemic administration of homeostatic γ-chain cytokines mediates antitumor responses in some patients treated with adoptive immunotherapy. Yet many patients experience toxic side effects. New work presented herein suggests these limitations can be overcome by membrane-tethering IL15 and IL21 to T-cell products.

Distinct host preconditioning regimens differentially impact the antitumor potency of adoptively transferred Th17 cells.

Background: Mechanisms by which distinct methods of host preconditioning impact the efficacy of adoptively transferred antitumor T helper cells is unknown.

Methods: CD4 T cells with a transgenic TCR that recognize TRP-1 melanoma antigen were polarized to the T helper 17 (Th17) phenotype and then transferred into melanoma-bearing mice preconditioned with either total body irradiation or chemotherapy.

Results: We found that preconditioning mice with a non-myeloablative dose of total body irradiation (TBI of 5 Gy) was more effective than using an equivalently dosed non-myeloablative chemotherapy (CTX at 200 mg/kg) at augmenting therapeutic activity of anti-tumor TRP-1 Th17 cells.

Shared and Unique Features of Human Interferon-Beta and Interferon-Alpha Subtypes.

Type I interferons (IFN-I) were first discovered as an antiviral factor by Isaacs and Lindenmann in 1957, but they are now known to also modulate innate and adaptive immunity and suppress proliferation of cancer cells. While much has been revealed about IFN-I, it remains a mystery as to why there are 16 different IFN-I gene products, including IFNβ, IFNω, and 12 subtypes of IFNα. Here, we discuss shared and unique aspects of these IFN-I in the context of their evolution, expression patterns, and signaling through their shared heterodimeric receptor.