2023
Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challenge
2021
Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.
Larkin J, Sarnaik A, Chesney J, Khushalani N, Kirkwood J, Weber J, Lewis K, Medina T, Kluger H, Thomas S, Domingo-Musibay E, Olah J, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Shi W, Wu R, Fardis M, Hamid O. Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy. Journal Of Clinical Oncology 2021, 39: 9505-9505. DOI: 10.1200/jco.2021.39.15_suppl.9505.Peer-Reviewed Original ResearchAnti-PD-1 therapyPrior anti-PD-1 therapyObjective response rateImmune checkpoint inhibitorsAdvanced melanomaPrimary resistanceAnti-PD-1 resistanceAnti-PD-1 responseBaseline tumor burdenDays of cyclophosphamideDays of fludarabineMedian cumulative durationMedian prior linesLong-term followAdoptive cell therapyStandard of careDetection of progressionNew safety risksDuration of exposureAutologous tumorMelanoma progressPrior therapyRECIST 1.1TIL productionCheckpoint inhibitors