SBIR-STTR Award

Major drawbacks associated with in vitro assays for sensitivity of tumors to specific chemotherapeutic drugs include the uncertainty of end point validity, the need for large tissue samples, and cost. Furthermore, these assays do not address the question of conversion of the drug to active moities by metabolic pathways in the host or alteration of drug activity by binding to plasma protein.It is proposed to develop a cell culture technology for growth and quantitation of tumor cells in small pore diffusion chambers which contain the tumor cells and protect them from the immune system of the immunologically unrelated host. In Phase I of the study, the manufacturing technologies and methods will be developed to reliably produce sterile cell growth chambers which can be easily utilized in the analytical laboratory. The optimum chamber size, cell inoculum, membrane characteristics, and materials for construction will be determined. Work planned for later phases of this program include(1) investigations of the growth characteristics of human tumors in cell growth chambers;(2) studies to determine if fibroblast overgrowth is a problemin this culture system and, if so, how it can best be prevented; (3) evaluation of the monolayer culture step in the proposed assay protocol with regard to both biological necessity and cost effectiveness; (4) evaluation of drug access to the interior of the chamber; and (5) development of an operating room kit which will enable the operating surgeon to begin processing the specimen at the time of surgical removal in order to increase the percentage of tumor specimens which can be grown in the cell culture system.The antineoplastic drug sensitivity assay which will be based on this cell culture system can be performed with the basic equipment and personnel available in most cell culture laboratories and requires a small number of tumor cells. Mass production of the diffusion chambers may make the assay less costly and faster than assays which do not involve exposure of tumor to drug in a living host and permit screening of new chemotherapeutic drugs against human tumors under physiological conditions.National Cancer Institute

Routine organization of a chemotherapy program based on test responses of the patient's tumor cells to proposed drugs has not been possible due to the lack of a practical, reliable laboratory test to define the most effective drug against a -specific tumor mass. Major drawbacks associated with in vitro assays for sensitivity of tumors to specific drugs include the uncertainty of end-point validity, the need for large tissue samples, cost, and the question of conversion of the drug to active moities by metabolic pathways or alteration of drug activity by binding to plasma protein.The technical and practical basis for a reliable, routine assay method and system may be found in the growth of tumor cells in small-pore diffusion chambers. The chambers, when implanted in rats, contain the cells, protect them from the cellular immune mechanisms of the rat host, and accommodate in vivo drug exposure of the patient's cells to the proposed antineoplastic drugs. In Phase I of the program the manufacturing technologies and methods have been developed to reliably produce sterile cell growth chambers that can be easily used. Phase 11 is organized to study the growth characteristics of human tumors in the chambers, to determine if fibroblast overgrowth is a problem, to evaluate. drug access to chamber interior, and to develop an operating room kit for preparing the test specimen at the time of surgical removal.The drug sensitivity test based on this cell culture system can be performed with the basic cell culture laboratory equipment and personnel and requires a small number of tumor cells for analysis.National Cancer Institute