Doctors can now draw T cells from a patient’s blood, modify them in a lab so they recognise cancer, and put them back. The treatment is called CAR T-cell therapy. A June 2024 review of the field describes it as strikingly successful against certain blood cancers, including acute lymphoblastic leukemia and large B-cell lymphoma.
It is one of several ways medicine now puts the immune system to work. Immunotherapy, also known as biological therapy, means treating disease by inducing, boosting or suppressing an immune response. Boosting is the aim in cancer. Suppression helps in autoimmune diseases, where the body attacks its own tissues.
How cancer immunotherapy works
The review lists three effects: slowing the growth of cancer cells, blocking the routes by which cancer spreads, and sharpening the immune system’s ability to recognise and destroy tumour cells.
Active approaches push the body’s own immune cells toward markers on a tumour, known as tumour-associated antigens. Passive ones hand the immune system extra parts, such as monoclonal antibodies, lymphocytes and cytokines. Some treatments combine the two.
Monoclonal antibodies are made by identical immune cells cloned from one parent cell. Each is built to latch onto a particular target on a cancer cell and flag it for destruction. Trastuzumab (Herceptin), which targets the HER2/neu protein, is used in breast and stomach cancer. Checkpoint inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo) work differently. They block the signals cancer cells use to hide from immune detection.
Other tools are older or stranger. Interferons slow the growth of cancer cells and activate immune cells, while interleukins stimulate the growth and activity of immune cells. Bacillus Calmette-Guerin, a live weakened strain of Mycobacterium bovis, is placed directly in the bladder to treat bladder cancer. It can also be used against malignant melanoma and certain leukemias.
Oncolytic virus therapy uses genetically modified viruses that infect and kill cancer cells. The cells burst, and the debris releases tumour antigens that set off a wider immune response. Talimogene laherparepvec (T-VEC), a modified herpes simplex virus, is used for melanoma.
Cancer vaccines come in two kinds. Preventive ones target cancer-causing viruses, and the HPV vaccine (Gardasil) and the HBV vaccine are examples. Therapeutic ones treat existing disease. Provenge, a dendritic cell vaccine, is used in advanced prostate cancer.
Designing vaccines from a genome
Reverse vaccinology turns the usual order around. Traditional vaccine work starts by growing the pathogen. This approach starts with its genetic sequence. Rino Rappuoli first described it in 2000.
Researchers sequence the pathogen’s genome and use software to predict which proteins sit on the surface or are secreted, since those are the ones the immune system can reach. Those proteins are cloned and produced in bacteria or yeast, then tested in animals, typically mice, to see whether they provoke an immune response. Strong candidates move to preclinical studies and then human trials.
The review credits the method with three advantages. It can find every potential protein antigen, including ones that are hard to isolate by conventional means. It is faster and cheaper because much of the work is computational. And it works on any pathogen whose genome has been sequenced.
Meningococcus B is the clearest success. No broadly protective vaccine existed for it because its capsule resembles human antigens. Reverse vaccinology picked out Factor H-binding protein, Neisserial adhesin A and Neisserial heparin-binding antigen, and all three are now part of MenB vaccines.
Other pathogens are at the candidate stage. Genome comparisons have flagged pilus proteins in group B and group A Streptococcus and in Streptococcus pneumoniae, surface proteins in Staphylococcus aureus, outer membrane proteins in E. coli and Chlamydia trachomatis, and 29 spore-specific proteins in Clostridium difficile.
The review expects both approaches to play a larger part in global health as the technology improves. Patients curious about any of these treatments should ask their own doctor what fits their situation. Consult your doctor for medical advice.
