Volume 31 of Issue 7 | Molecular therapy : the journal of the American Society of Gene Therapy
Authors: Cieniewicz B, Bhatta A, Torabi D, Baichoo P, Saxton M, Arballo A, Nguyen L, Thomas S, Kethar H, Kukutla P, Shoaga O, Yu B, Yang Z, Fate M, Oliveira E, Ning H, Corey L, Corey D
To leverage complementary mechanisms for cancer cell removal, we developed a novel cell engineering and therapeutic strategy co-opting phagocytic clearance and antigen presentation activity into T cells. We engineered a chimeric engulfment receptor (CER)-1236, which combines the extracellular domain of TIM-4, a phagocytic receptor recognizing the "eat me" signal phosphatidylserine, with intracellular signaling domains (TLR2/TIR, CD28, and CD3ζ) to enhance both TIM-4-mediated phagocytosis and T cell cytotoxic function. CER-1236 T cells demonstrate target-dependent phagocytic function and induce transcriptional signatures of key regulators responsible for phagocytic recognition and uptake, along with cytotoxic mediators. Pre-clinical models of mantle cell lymphoma (MCL) and EGFR mutation-positive non-small cell lung cancer (NSCLC) demonstrate collaborative innate-adaptive anti-tumor immune responses both in vitro and in vivo. Treatment with BTK (MCL) and EGFR (NSCLC) inhibitors increased target ligand, conditionally driving CER-1236 function to augment anti-tumor responses. We also show that activated CER-1236 T cells exhibit superior cross-presentation ability compared with conventional T cells, triggering E7-specific TCR T responses in an HLA class I- and TLR-2-dependent manner, thereby overcoming the limited antigen presentation capacity of conventional T cells. Therefore, CER-1236 T cells have the potential to achieve tumor control by eliciting both direct cytotoxic effects and indirect-mediated cross-priming.
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Clinical liver disease
Authors: Morris MD, McDonell C, Kim RG, Laguardia Y, Kanner R, Price JC
medRxiv : the preprint server for health sciences
Authors: Middha P, Thummalapalli R, Betti MJ, Quandt Z, Balaratnam K, Cardenas E, Falcon CJ, Faleck DM, Princess Margaret Lung Group, Gubens MA, Huntsman S, Kachuri L, Khan K, Li M, Lovly CM, Murray MH, Patel D, Werking K, Zhan LJ, Liu G, Aldrich MC, Schoenfeld AJ, Ziv E
Chronic obstructive pulmonary diseases (Miami, Fla.)
Authors: Barjaktarevic I, Cooper CB, Shing T, Buhr RG, Hoffman EA, Woodruff PG, Drummond MB, Kanner RE, Han MK, Hansel NN, Bowler RP, Kinney GL, Jacobson S, Morris MA, Martinez FJ, Ohar J, Couper D, Tashkin DP
Arthritis research & therapy
Authors: Braun J, Blanco R, Marzo-Ortega H, Gensler LS, Van den Bosch F, Hall S, Kameda H, Poddubnyy D, van de Sande M, van der Heijde D, Zhuang T, Stefanska A, Readie A, Richards HB, Deodhar A
American journal of respiratory and critical care medicine
Authors: Bowerman C, Bhakta NR, Brazzale D, Cooper BG, Cooper J, Gochicoa-Rangel L, Haynes J, Kaminsky DA, Lan LTT, Masekela R, McCormack MC, Steenbruggen I, Stanojevic S
Hepatology (Baltimore, Md.)
Authors: Mehta N, Kelley RK, Yao FY
JAMA
Authors: Thakur N, Martinez A
Chronic obstructive pulmonary diseases (Miami, Fla.)
Authors: Arjomandi M, Zeng S, Chen J, Bhatt SP, Abtin F, Barjaktarevic I, Barr RG, Bleecker ER, Buhr RG, Criner GJ, Comellas AP, Couper DJ, Curtis JL, Dransfield MT, Fortis S, Han MK, Hansel NN, Hoffman EA, Hokanson JE, Kaner RJ, Kanner RE, Krishnan JA, Labaki W, Lynch DA, Ortega VE, Peters SP, Woodruff PG, Cooper CB, Bowler RP, Paine R, Rennard SI, Tashkin DP, and the COPDGene and SPIROMICS Investigators
Chronic obstructive pulmonary diseases (Miami, Fla.)
Authors: Izquierdo M, Marion CR, Genese F, Newell JD, O'Neal WK, Li X, Hawkins GA, Barjaktarevic I, Barr RG, Christenson S, Cooper CB, Couper D, Curtis J, Han MK, Hansel NN, Kanner RE, Martinez FJ, Paine R, Tejwani V, Woodruff PG, Zein JG, Hoffman EA, Peters SP, Meyers DA, Bleecker ER, Ortega VE, National Heart, Lung and Blood Institute’s SubPopulations and InteRmediate Outcome Measures In COPD
