Drug Discovery Opinion

Both HIV and cancer cells have found ways to evade the body’s immune system but researchers at Yale University have now found a way to boost the body’s ability to fight HIV and cancer. The team have identified bifunctional small molecules, termed “antibody-recruiting molecule targeting HIV” (ARM-H) and “antibody-recruiting molecule targeting prostate cancer” (ARM-P), which bind simultaneously to antibodies and to proteins on HIV, HIV-infected cells or cancer cells.

ARM-H molecules bind to gp120, a component of the Env glycoprotein on the surface of HIV and virus-infected cells and to anti-2,4-dinitrophenyl antibodies already present in the bloodstream. The ternary complex formed between the antibody, ARM-H, and gp120 is immunologically active, and leads to complement-mediated destruction of Env-expressing cells. ARM-H also prevents virus entry into human T-cells and so has the potential to inhibit viral replication by two mutually reinforcing mechanisms.

ARM-P molecules bind with high affinity to prostate-specific membrane antigen (PSMA) and, by inducing complexes of anti-2,4-dinitrophenyl antibodies with prostate cancer cells, mediate antibody-dependent killing of the cancer cells.

The team has begun to evaluate the ARM molecules in mice, and hope that the strategy of using antibody-recruiting small molecules to boost the immune response will prove useful for treating HIV, cancer, and other diseases.

Both studies are published in the Journal of the American Chemical Society (ARM-H and ARM-P).

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