Research in the cancer immunotherapy project has progressed as anticipated and outlined in our last year's report. Our work this year was well accepted by researchers from the experimental disciplines, and the methods we have developed are sought after by clinicians and drug developers.

Thus, our mathematical model for alloreactive cytotoxic T cell immunotherapy for brain cancer will be used, in conjunction with the clinical results of an NIH trial headed by C. Kruse and L. Liau, to develop a new method for personalizing immunotherapy in brain cancer. We will identify the predictive model parameters and measurable biomarkers whose levels influence the predictive parameters, e.g. volumetric data of tumor, mass, of cytokines, and of cell surface receptors. This information will serve for constructing and validating a new personalization model for brain cancer immunotherapy, based on a mathematical model with clinically evaluated individual biomarkers. Such a personalization model could provide a reliable method for identifying optimal individualized treatments. Additional collaborations with clinicians, novel immunotherapy methods for brain cancer are underway.

Our published mathematical model for the new cancer immunomodulatory protein interleukin 21 (IL-21) was challenged by the developer of this drug (Novo Nordisk), suggesting that validation of our published model by their own preclinical results would pave the way for the use of our model in the clinical development of the drug. Thus, we set upon ourselves to advance the model into a full systemic pharmacokinetic/pharmacodynamic model, and to validate its accuracy in the preclinical setting provided by Novo Nordisk. Our model was successful in retrieving tumor growth curves, under various IL-21 treatment regimens, in wild-type and immuno-deficient mice bearing different solid tumor diseases. Moreover, the model suggests that regimens with significantly lower dose intensity, and therefore less drug-associated toxicity, can be as efficacious as those previously tested. We intend to adjust the model to the clinical setting, thereby using it to streamline the clinical development of this drug.

Interesting developments also occur in our cancer stem cell project. Collaborations with our European partners begin to show fruit and our biomathematical work, concerning the behavior of breast cancer stem cells has ripened into a set of very interesting, and hopefully important, predictions. Recently, we have been invited by the American Association of Cancer Research, AACR, to deliver a short lecture in an AACR International Conference on “Advances in Cancer Research: From the Laboratory to the Clinic,” which took place in Jordan on March 16-20, this year. Our presented research concerned a new therapy method, which employs the mathematical understanding we had been developing over the years, for pinpointing a certain protein, expected to divert cancer stem cells to terminal differentiation.

The AACR meeting, held in the Middle East for first time, was interesting, both scientifically and geopolitically. World leading cancer scientists discussed their recent achievements, both in laboratory and in clinical research, and contributed works were also interesting. However, the atmosphere in the conference was politically influenced and I believe that many more such opportunities have to be created for establishing good scientific relationships in the area. Powerful scientific authorities, such as AACR, also need to exercise their obligations in guaranteeing scientific freedom. This, I believe, will accelerate the rate of normalization, at least among scientist of different origins.

I thank you once more for your ongoing support of IMBM’s activity, and wish you a productive activity year.

  Zvia Agur