G1-4 A, an arabinogalactan polysaccharide from Tinospora cordifolia increases dendritic cell immunogenicity in a murine lymphoma model.
The immunogenicity of dendritic cells (DC) is known to increase with their maturation state and both are induced by microbial products like LPS. In this study, we have investigated the effect of G1-4A, a polysaccharide isolated from Indian medicinal plant, Tinospora cordifolia on phenotypic and functional maturation of murine bone marrow derived dendritic cells (BMDC) and its ability to be used as an adjuvant in immunotherapy. G1-4A, enhanced surface expression of CD40, CD80, CD86, MHCII by BMDC in vitro and splenic DC in vivo. T cell allostimulatory activity and secretion of IL-12 and TNFα by BMDC were also increased. Treatment with G1-4A resulted in decreased phagocytosis and increased antigen processing that are characteristic of mature DC. G1-4A treated DC cross presented exogenous antigens on a MHC I background which resulted in the activation of cytotoxic T cells. These cells thus activated could cause lysis of target tumor cells in vitro. Administration of tumor lysate pulsed G1-4A treated DC resulted in decreased tumor burden in preventive as well as therapeutic tumor challenge experiments in a murine lymphoma model. These results thus confirm that G1-4A could be a promising nontoxic maturation agent to be potentially used in DC based immunotherapy of tumor.
Radiation Biology and Health Sciences Division, Bio-Medical Group, Bhabha Atomic Research Centre, Mumbai 85, India.
Vipul K
VK
Pandey
Bhavani S
BS
Shankar
Krishna B
KB
Sainis
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007111:Immunity, Cellular; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D031610:Tinospora / Q000378:metabolism*
D015703:Antigens, CD; D000970:Antineoplastic Agents; C542611:G1-4A polysaccharide; D011134:Polysaccharides