Synergistic anti-tumor effect of Allocetra-OTS in combination with immune checkpoint inhibitors (ICI)/chemotherapy/CAR T, through in-vivo reprogramming of macrophages
Annals of Oncology
; 33:S759, 2022.
Article
in English
| EMBASE | ID: covidwho-2041531
ABSTRACT
Background:
ICI revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Here we investigated the anti-tumoral effect of Allocetra—OTS cellular therapy, in solid tumor models.Methods:
Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis.Balb/c mice were inoculated in the peritoneal cavity with AB12 (mesothelioma) stably transduced with pLenti-PGK-V5-Luc-Neo for IVIS visualization and treated with anti-CTLA4, anti-PD1, or cisplatin, with or without Allocetra-OTS (also administered as monotherapy). Kaplan-Meier log rank test was done for survival. CAR T model was induced in SCID-Bg mice were inoculated intraperitoneally with human HeLa-CD19, followed by treatment with 10×109 cells of Allocetra-OTS or vehicle, and 1×107 CD19-CAR T cells or mock T cells.Results:
Anti-CTLA4 therapy significantly improved survival from mean 34±9 to 44.9 ±20 days (p<0.05). However, Allocetra-OTS monotherapy improved survival to 52.3 ±20 days (p<0.02) and anti-CTLA4 + Allocetra-OTS combination therapy to 86.7±20 days (p<0.0001) with complete cancer remission in 60-100% of mice. Similar results were seen in combination therapy with either anti-PD1 or cisplatin. In the CAR-T model, SCID-Bg mice survived 30±5 days (range 27–37) and were sacrificed or died from tumor progression. Results were verified using IVIS of intraperitoneal HeLaCD19-Luc cells. 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 intraperitoneal tumor progression, Allocetra-OTS as monotherapy 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 is planned for Q3 2022, and 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. Legal entity responsible for the study The authors.Funding:
Enlivex Therapeutics Ltd. Disclosure D. Mevorach Financial Interests, Personal, Royalties, Founder & CSO Enlivex Therapeutics LTD. E. Yalon, E. Regev, C. Ankri, O. Hershkovitz, Y. Shabat, B. Reicher Financial Interests, Personal, Full or part-time Employment Enlivex Therapeutics LTD.
CD19 antigen; cisplatin; cytotoxic T lymphocyte antigen 4; endogenous compound; immune checkpoint inhibitor; AB1-2 cell line; adult; animal cell; animal experiment; animal model; antineoplastic activity; apoptosis; Bagg albino mouse; cancer combination chemotherapy; cancer model; cancer patient; cancer regression; cancer size; cancer survival; cell therapy; chemotherapy; chimeric antigen receptor T-cell; chimeric antigen receptor T-cell immunotherapy; conference abstract; controlled study; coronavirus disease 2019; drug combination; drug potentiation; drug safety; drug therapy; human; in vivo study; log rank test; macrophage; male; mesothelioma; monotherapy; mouse; nonhuman; parttime employment; peritoneal cavity; phase 1 clinical trial; SCID beige mouse; sepsis; solid malignant neoplasm; T lymphocyte; tumor growth
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
Language:
English
Journal:
Annals of Oncology
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS