Your browser doesn't support javascript.
Synergistic Anti-Tumor Effect of Allocetra-Ots, a Cellular Immune-Therapy, in Combination with Immune Checkpoint Inhibitors/ Chemotherapy/Car T, through in-Vivo Reprogramming of Macrophages
Journal for ImmunoTherapy of Cancer ; 10(Supplement 2):A1432, 2022.
Article in English | EMBASE | ID: covidwho-2161960
ABSTRACT
Background Immune checkpoint inhibitors (ICI) revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Allocetra-OTS has an immune modulating effect on macrophages1 and showed an excellent safety profile in patients including patients with sepsis.2 Here we investigated the anti-tumoral effect of Allocetra-OTS cellular therapy, in solid tumor animal models. Methods Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis. In an immunecompetent model, Balb/c mice were inoculated intraperitoneally (IP) with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti-CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical score and weekly using IVIS. Kaplan-Meier log rank test was done for survival. For Allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis.To follow tumor growth in vivo, HeLa-CD19 cells were stably transduced with pLenti-PGK-V5-Luc-Neo. For CAR preparation, fresh mononuclear cells (MNC) were transfected with CD19-CAR plasmids. SCID-Bg mice were injected IP with human HeLa-CD19 or HeLa-CD19-luciferase cells, 10x10 allocetraOTS or vehicle, and 10x10 CD19-CAR T cells or mock T cells. Results In immune competent Balb/c mesothelioma model, anti-CTLA4 standalone therapy significantly improved survival from mean 34+/-9 to 44.9 +/-20 days (p<0.05). Similarly, Allocetra- OTS standalone therapy improved survival to 52.3 +/-20 days (p<0.02). However, anti-CTLA4 + Allocetra-OTS combination therapy, ameliorated survival to 86.7+/-20 days (p<0.0001) with complete cancer remission in 60-100% of mice (figure 1 & 2). Similar anti-tumoral effects of Allocetra- OTS were seen in mesothelioma model in a combination therapy with either anti-PD1 or cisplatin. In the CAR-T model, SCID-Bg mice were sacrificed or died from tumor progression in 30+/-5 days (range 27-37). CAR T cell therapy significantly improved survival to 55+/-11 days (p < 0.05 vs MOCK) but Alloctra-OTS further improved survival to 75+/-10 (p < 0.001) with 20-40% complete remission. Conclusions During IP tumor progression, Allocetra-OTS as a standalone therapy or in combination with ICI, cisplatin or CAR-T therapy, significantly reduced tumor size and resulted in complete remission in up to100% treated mice. Based on excellent safety profile in > 40 patients treated in prior clinical trials for sepsis and Covid-19, Phase I/II clinical trial of Allocetra-OTS plus chemotherapy has started and first patient already recruited. A second Phase I/II clinical trial of Allocetra-OTS plus anti-PD1, as a second- and third-line therapy in various cancers, is planned for Q4 2022.
Keywords

Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Experimental Studies Language: English Journal: Journal for ImmunoTherapy of Cancer Year: 2022 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Experimental Studies Language: English Journal: Journal for ImmunoTherapy of Cancer Year: 2022 Document Type: Article