Combining conventional therapies with intratumoral injection of autologous dendritic cells and activated T cells to treat patients with advanced cancers.
Dendritic cells (DCs) are potent antigen-presenting cells that have been used in cancer immunotherapy. To take advantage of the ability of DCs to acquire antigenic materials from their environment and generate primary as well as recall immune responses, 37 patients with advanced cancers were enrolled in a series of protocols based on direct intratumoral injection of immature DCs. To augment antigen uptake and antitumor immune response, DC injection was combined with radiotherapy or chemotherapy and/or injection of activated T cells. Treatments were well tolerated with no adverse reactions. Clinical responses were based on Response Evaluation Criteria in Solid Tumors, with the majority of patients showing stable disease. One of two patients who also received local radiation achieved a sustained complete response at injected and metastatic sites. The clinical responses observed in cancer patients with advanced disease suggest potential effectiveness of combination strategies and establish the basis for the current treatment protocol that is underway.
Mann
Dean L
DL
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. dmann001@umaryland.edu
Celluzzi
Christina M
CM
Hankey
Kim G
KG
Harris
Kristina M
KM
Watanabe
Ryuko
R
Hasumi
Kenichiro
K
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000637:transplantation; D015703:Antigens, CD / Q000032:analysis; D001943:Breast Neoplasms / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology; D003131:Combined Modality Therapy; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D013274:Stomach Neoplasms / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014182:Transplantation, Autologous
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D006684:HLA-DR Antigens