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.