Researchers have found that a promising new cancer therapy is extremely potent against one of the world's most devastating infectious diseases: tuberculosis (TB). Scientists at Texas Biomedical Research Institute (Texas Biomed) in the US found the therapy dramatically reduces TB growth, even for bacteria that are drug-resistant.
The findings, reported in the journal Biomedicine & Pharmacotherapy, were made in novel cellular models featuring TB-infected human cells that can help accelerate screening of potential TB drugs and therapies like this one.
The therapy combines two molecules – one of which is already FDA-approved for use in cancer patients, and another that is being evaluated in Phase 1/2 clinical trials for cancer. The compounds help the body initiate its normal cell death processes in targeted areas, be it cancerous cells, or in this case, cells infected with Mycobacterium tuberculosis (M.tb), the bacteria that causes TB.
"Immunotherapy has been a game changer in the cancer field by finding ways to help a patient’s own immune system fight tumors more effectively," said Larry Schlesinger, Professor, President and CEO at Texas Biomed.
"We believe that, similarly, host-directed therapies can be a game changer for infectious diseases," he added. TB accounts for more than 1.6 million deaths worldwide every year. The bacterium primarily infects the lungs.
Patients must take antibiotics for months to bring active infection under control; drug resistance is on the rise, making treatment even more challenging. M.tb blocks a normal cell death process called apoptosis. This allows the bacteria to grow inside immune cells in the lungs, called alveolar macrophages.
The new study shows that by inhibiting two key proteins, MCL-1 and BCL-2, M.tb can no longer hijack the apoptosis process and macrophages are able to kill M.tb. The team tested MCL-1 and BCL-2 inhibitors individually, together and in combination with TB antibiotics to see how TB growth was affected.
Using both inhibitors was more effective at limiting TB growth than just one or the other; and combining them with antibiotics was far more effective than either inhibitors or antibiotics alone, the study showed.