Showing papers by "Mary J. Fidler published in 2020"
Rutgers University1, Rush University Medical Center2, Columbia University3, Vanderbilt University Medical Center4, Franciscan Health5, Ohio State University6, Harvard University7, St. Jude Children's Research Hospital8, University of Tennessee Health Science Center9, Brigham and Women's Hospital10, Massachusetts Institute of Technology11, Washington University in St. Louis12
TL;DR: It is reported that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts “cold” tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade, and proposes that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.
Abstract: Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated “hot” tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts “cold” tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.
122 citations
Sarah Cannon Research Institute1, Harvard University2, Rush University Medical Center3, University of California, Los Angeles4, University of Chicago5, Indiana University6, Memorial Sloan Kettering Cancer Center7, Yale University8, University of Barcelona9, University of Texas MD Anderson Cancer Center10
TL;DR: CX-2009 is a PROBODY drug conjugate directed against CD166 (ALCAM) and conjugated to DM4, a potent microtubule inhibitor (MTI) which is overexpressed in carcinomas but is also...
Abstract: 526Background: CX-2009 is a PROBODY drug conjugate (PDC) directed against CD166 (ALCAM) and conjugated to DM4, a potent microtubule inhibitor (MTI). CD166 is overexpressed in carcinomas but is also...
11 citations
TL;DR: This data indicates that the combination of nivolumab/ipilimumab with PD-1/PD-L1 inhibition after chemoradiation (CRT) for unresectable stage III NSCLC improves overall survival.
Abstract: 9010Background: Consolidation PD-1/PD-L1 inhibition after chemoradiation (CRT) for unresectable stage III NSCLC improves overall survival. In stage IV NSCLC, the combination of nivolumab/ipilimumab...
9 citations
1 citations
TL;DR: This data indicates that TSP9083 has the potential to significantly improve the prognosis for small cell lung cancer patients with a poor prognosis and the high unmet need for checkpoint inhibitor treatment.
Abstract: TPS9083Background: Despite several recent checkpoint inhibitor approvals extensive stage small cell lung cancer (SCLC) is associated with a poor prognosis and remains an area of high unmet need. RR...
1 citations