Microencapsulated tumor assay: new short-term assay for in vivo evaluation of the effects of anticancer drugs on human tumor cell lines.
A new in vivo has been developed for evaluating the antitumor activity of chemotherapeutic drugs. The assay is based on a microencapsulation technology developed by Damon Biotech, Inc., Boston, MA, which makes it possible to encapsulate human tumor cells in small (about 1 mm in diameter) microcapsules with semipermeable membranes. Microcapsules containing human tumor cells were injected i.p. into nude or C57BL/6 mice and drugs were administered i.v. The microcapsules were recovered at various intervals following treatment and determinations of drug effects were made based on the differences in the number of tumor cells recovered from the treated and nontreated animals. Using this assay we found that (a) encapsulated tumor cells grew better in the in vivo system than in vitro under the conditions tested; (b) drugs crossed the capsular membrane and killed or inhibited the proliferation of tumor cells; and (c) the antitumor effect was consistent with the relative therapeutic efficacy of drugs or level of resistance of tumor cells detected by other in vitro or in vivo tests. The tumor microencapsulation assay offers several properties which make it attractive for use in new drug development: (a) the antitumor activity of drugs can be tested against human tumor cells under conditions which provide for three-dimensional growth and in vivo supply of nutrients; (b) the sensitivity of tumor cells can be assessed following exposure to drugs at concentrations which are achievable in vivo; (c) compounds requiring in vivo metabolic activation can be tested; (d) the effect of each drug injection can be quickly evaluated; (e) inhibition of tumor cell proliferation versus cytoreductive effects of drugs can be discriminated; (f) the test is applicable to virtually all histological types of human tumor cells; and (g) the tumor microencapsulation assay is a short-term, simple, and relatively inexpensive assay.
Gorelik
E
E
Damon Biotech, Inc., Boston, Massachusetts 02194.
Ovejera
A
A
Shoemaker
R
R
Jarvis
A
A
Alley
M
M
Duff
R
R
Mayo
J
J
Herberman
R
R
Boyd
M
M
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013370:Subrenal Capsule Assay; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil