Enhancing Anticancer Activity Through Computer Modeling

Cancer immunologists used a computer modeling system to predict and manipulate the cancer fighting ability of populations of tumor-infiltrating lymphocytes isolated from metastatic melanoma patients.

Tumor-infiltrating lymphocytes (TILs) are heterogeneous cell populations that form an interconnected network that determines their collective reactivity against tumors. TILs are used in adoptive cell transfer therapy, where they are removed from a metastatic melanoma patient's tumor and evaluated for their antitumor activity. TILs that show the strongest antitumor response are expanded and then reinjected back into the patient.

In the current study investigators at the Technion-Israel Institute of Technology (Haifa, Israel) sought to understand why some TILs possessed more potent anticancer potential than others. To this end they used flow cytometry measurements to establish the characteristics of the immune cells within 91 TILs removed from 27 metastatic melanoma patients. Results of this study showed that each TIL comprised several different subpopulations of immune cells, with each subpopulation distinguished by a particular set of chemical markers on the cell surfaces. This data enabled the investigators to develop a system of computational modeling that established a set of rules to predict which TILs would show the most antitumor activity based on their particular combination of subpopulations.

Information obtained from the modeling system enabled the investigators to prepare TILs that were particularly potent or particularly inactive. Results published in the April 28, 2009, online edition of the journal Molecular Systems Biology revealed that in 12 nonreactive TILs taken from four patients, the investigators were able to induce a 106-fold increase in TIL antitumor activity by expanding an optimal blend of subpopulations within the TIL.

"The computational tools we developed allowed us to predict whether a TIL culture will respond to the tumor with an accuracy of more than 90%," said senior author Dr. Yoram Reiter, professor of biology at the Technion. "This enabled us to turn nonreactive TILs into reactive ones and vice versa. We need to expand the samples that we have tested from more patients, followed by more examples on TIL cultures that can be transformed from nonreactive to reactive."

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Technion-Israel Institute of Technology