Tumor tissue recycling--a new combination treatment for solid tumors: experimental and preliminary clinical research.
Although H&H combination treatment (high active TIL and high sensitive drugs) as previously described to solid tumor patients is more efficient than single-agent treatments such as TIL adoptive immunotherapy, it has a short-term efficiency for the immune response to metastatic cancers. Currently, a new version of the combination of active and adoptive immune response was established. TILs, tumor vaccines and high sensitive drugs. The experimental results demonstrated that TILs from 49 cases (65%) were more than 1,000 expansion-fold and only 6 cases (24%) less than 500 fold. The peaks of TIL 3H-TdR cytotoxicity test from 35 of 64 TIL specimens were kept from 40 to 56 days. TIL phenotypes studied here indicated CD3 80 +/- 21%, CD4 37 +/- 21%, CD8 44 +/- 18% and HLA DR 69 +/- 24% after IL2 induction, in contrast, to CD3 20 +/- 12%, CD4 10 +/- 7%, CD8 11 +/- 3% and HLA DR 30 +/- 16% before induction. Thirty two of 75 cases were assayed using the chemosensitivity test. The distribution of positive rates for the chemosensitivity test were slightly different in different tumors regarding tissues in liver, lung, ovary, breast, and melanoma, 2 cases with melanoma all showed negative results. The results of a tumor vaccine using TNF-alpha gene transduction demonstrated that the expression of HLA Class I and HLA Class II were dramatically increased 87% and 43%. After implanting tumor cells via transduced TNF-alpha retroviral vector into 6-12 week old BALB/c nude mice, only one subject of nine nude mice had a tumor weight of 2.67 g, but the control group all displayed tumors with a weight of 3.24 +/- 0.56 g. Preliminarily clinical trials also showed that the new version was obviously a promising combination.
Li
B
B
Rush Cancer Institute, Rush University, Chicago, IL 60612, USA. Bli@rush.edu
Ding
J
J
Larson
A
A
Song
S
S
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha