Antibody Drugs Customized by Genotype

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The next step is to develop a portfolio of antibodies that are customized for each group of patients within the matrix. The drugs would be altered slightly so that they can bind specifically to the receptors in patients of each genotype. Ramakrishnan says that the portfolio could consist of a minimum of four and a maximum of nine drugs (one for each group) to achieve a high response rate in each group.

The approach is different from "personalized" medicine that is tailored to an individual. Instead, Ramakrishnan says, this "stratified" approach offers some personalization but in a more manageable way. He believes that a stratified approach to monoclonal-antibody therapies can offer advantages to pharmaceutical companies. If they begin stratifying patients in clinical trials, they could achieve better results and help justify the treatments to regulatory agencies and insurers, he says. Companies could also put a higher premium on drugs if those drugs came with theragnostic tests.

PIKAMAB hopes to work with pharmaceutical companies to create commercial theragnostic tests and stratified therapies involving drugs that are already on the market or in development. Together, they also plan to develop their own monoclonal antibodies.

"I think it's useful to have a predictive test that can accurately describe whether a particular individual has a receptor that will make ADCC easier or harder to exploit as an anti-tumor mechanism," says Louis Weiner, a cancer immunologist at Georgetown University who has no ties to PIKAMAB. Weiner is, however, skeptical that customized antibodies are necessary to improve monoclonal-antibody therapies. He sees more potential in "high affinity" monoclonal antibodies that bind tightly to immune cells regardless of a patient's genotype.

Ramakrishnan argues that such drugs may not completely optimize the responses of all genotypes, and that there is room for further improvement with customized drugs. He points out that when monoclonal antibodies are used to treat cancer, it is usually in combination with radiation or other treatment. By optimizing the drugs, he says, it may be possible that certain patients could receive them as stand-alone therapies, thereby reducing the side effects and cost of treatment.