Biology subjects

Mullinax, J.

Publications and source records attributed to Mullinax, J..

3 recordsLinked to original sources

bioRxiv2026

Lymphoma response to chimeric antigen receptor T cell therapy is driven by endogenous tumor-reactive CD8⁺ T cells

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy induces durable remissions in a subset of patients with relapsed or refractory large B-cell lymphoma; however, most patients fail to respond or eventually relapse. By integrating whole-genome and transcriptome profiling of 54 patients with functional assays, syngeneic models, and mathematical modeling, we demonstrate that durable CAR-T efficacy requires cooperation between CAR-T cells and endogenous CD8 (eCD8) T cells recruited to join the attack on malignant cells. Tumors with biallelic loss of MHC class I or CD58 exhibited high genomic complexity, increased neoantigen burden, and resistance to CAR-T therapy. MHC-I-deficient lymphomas showed suboptimal response in immunocompetent hosts compared to wild type. Importantly, sustained responses in mice occurred only in the presence of eCD8 cells, whereas all CD8-depleted mice relapsed after initial CAR-T-mediated tumor regression. Patients and murine ELISPOT assays confirmed enhanced endogenous T-cell activation post-CAR-T. These findings reveal that CAR-T therapy functions not only as a cytotoxic modality but also as a catalyst for endogenous anti-tumor immunity.

cancer biology↗

bioRxiv2024

A systematic review of laboratory investigations into the pathogenesis of avian influenza viruses in wild avifauna of North America

The lack of consolidated information regarding wild bird species response to avian influenza virus (AIV) infection is a challenge for conservation managers, researchers, and related sectors such as public health and commercial poultry. Such information could be used to model complex disease dynamics within communities, prioritize species for surveillance and conservation efforts, or identify species more likely to facilitate spillover into domestic animals or humans. Using two independent searches, we reviewed published literature for studies describing wild bird species experimentally infected with avian influenza to assess host species relative susceptibility to AIVs. Additionally, we summarized broad-scale parameters for elements such as shedding duration and minimum infectious dose that can be used in transmission modeling efforts. Our synthesis documented that waterfowl (i.e., Anatidae) comprise the vast majority of published AIV pathobiology studies, whereas gulls and passerines were less represented in research despite evidence that they also are susceptible and contribute to high pathogenicity avian influenza disease dynamics. This study represents the first comprehensive effort to compile available literature regarding the pathobiology of AIVs in all wild birds in over a decade. This database provides an opportunity to critically examine and assess what is known and identify where further insight is needed.

ecology↗

bioRxiv2016

Harnessing the lymphocyte meta-phenotype to optimize adoptive cell therapy

There is an urgent need for reliable effective therapy for patients with metastatic sarcoma. Approaches that manipulate the immune system have shown promise for patients with advanced, widely disseminated malignancies. One of these approaches is adoptive cell therapy (ACT), where tumor-infiltrating lymphocytes (TIL) are isolated from the tumor, expanded ex vivo, and then transferred back to the patient. This approach has shown great promise in melanoma, leading to an objective response in approximately half of treated patients [14]. Standard protocols involve characterization of TIL populations with respect to adaptive CD4+ and CD8+ T-lymphocytes, but neglect the possible role of the innate lymphoid repertoire. Due to toxicity and the high cost associated with ACT, the IFN-{gamma} release assay is currently used as a proxy to identify suitable TIL isolates for ACT. Efforts in TIL-ACT for sarcoma, which are pre-clinical and pioneered at Moffitt Cancer Center, have shown that only a minority of the TIL cultures show tumor specific activity in ex vivo IFN-{gamma} assays. Surprisingly, internal melanoma trial data reveal a lack of correlation between IFN-{gamma} assay and clinical outcomes, highlighting the need for a more reliable proxy. We hypothesize the existence of a predictable TIL meta-phenotype that leads to optimal tumor response. Here, we describe preliminary efforts to integrate prospective and existing patient data with mathematical models to optimize the TIL meta-phenotype prior to re-injection.

cancer biology↗