Cancer

　　 Immune System Promises Complete Tumor Elimination •Intact immunity of cancer patients •It can be directed to target cancer cells •Immunotherapy is a highly desirable alternative to current therapies Proof-of-concept for Cancer Immunotherapy

Current Status of Immunotherapy Development •Peptide/tumor lysate-pulsed DC cells •Cytokine mediated immunotherapy •Tumor-infiltrating lymphocytes (TILs) •Engineered T cells to express tumor associated antigen (TAA) •Naked DNA •Recombinant virus Despite the poor clinical results, dozens of cancer vaccine clinical trials are currently being conducted by both industrial and academic sponsors. •Highly demanding •Little cytotoxicity FDA Approval of Cell therapy

Flaws in Cancer Vaccine Development •Preventive immunity v. therapeutic immunity •Unique tumor antigen v. a set of tumor antigen •Tumor-specific antigens (TSAs) v. tumor associated antigens (TAAs) Is cancer a disease of weakened immune system? Immune Status of Cancer Patients •Most of cancer patients are immunocompetent individuals •Diverse leukocyte infiltration of tumors •The stronger immune response, the faster tumor growth Right versus Wrong Immune Response to Tumor Balance btw two polarised immune response Th2 Tumor Microenvironment

Type 2 cytokines down-regulate •MHC expression •Co-stimulatory molecules •Regulatory T attraction Th1 Tumor Environment

Type I cytokines up-regulate •MHC expression of tumor •Co-stimulatory molecules •Non-specific killing Immunogenicity of BCL1

Tumor-mediated Immunoavoidance

A successful immunotherapy requires

1. Conversion of Th2 immune response to Th1 response
2. Breaking immunotolerance of tumor