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Cancer immunotherapy refers to treatments that make the body’s immune system better at fighting tumors. Researchers believe these approaches could dramatically improve prospects for patients, which is why the latest clinical data will be closely scrutinized at the annual meeting of the American Society of Clinical Oncology under way this week end.
But it is a broad church. Researchers are exploring all sorts of strategies to overcome stealth tactics used by tumor cells and to enhance the body’s own immune response. And it remains to be seen which will win out in the end or whether combination therapies could create more powerful effects. Here’s a round-up of approaches taken by numerous drug makers, compiled with the help of Datamonitor Healthcare.
Checkpoint inhibitors: The body has a number of natural “brakes” on the immune system to prevent it going into overdrive and attacking healthy tissue. But many tumor types “trick” the immune system into applying the brakes in order to evade detection. And so biochemical interactions that dampen down an immune response are known as “checkpoints.”
Drug makers are developing a class of therapies known as checkpoint inhibitors that target these pathways, lifting the foot off the brakes. Only two immunotherapies have been approved so far, and one fits into this category. Yervoy, a drug developed by Bristol-Myers Squibb BMY +3.17%, disables a substance known CTLA-4 which halts the activation of T-cells, those responsible for killing tumor cells. It was approved as a treatment for metastatic melanoma in 2011.
Another target is a protein found on the surface of cancer cells, known as PD-L1, which is used by tumors to “hide” from the immune system. It works by binding with a receptor on T-cells called PD-1. Drugs that target either PD-1 or PD-L1 can interrupt the interaction, revealing the tumor to the immune system and stimulating a stronger response. These drugs are expected to form the next wave of cancer immunotherapies since they have been shown to have a better safety profile than CTLA-4 inhibitors.
Companies working on this approach include Agenus; Alnylam Pharmaceuticals; AnaptysBio; AstraZeneca AZN.LN -1.41%; Aurigene DiscoveryTechnologies; Bristol-Myers Squibb; Fortress Biotech; GlaxoSmithKline; Kadmon Pharmaceuticals; KAHR Medical; Medivation; Merck; Merck KGaA; Pierre Fabre Medicament; Regeneron Pharmaceuticals; Roche; Sorrento Therapeutics SRNE -3.73%; Sutro Biopharma and Tesaro.
TNF receptor agonists: If checkpoint inhibitors take the foot off the brakes, TNF receptor agonists press the accelerator. This class of drugs activates biochemical pathways that stimulate a stronger immune response. The two TNF receptors being targeted by drug maker are known as OX40 and CD40. Research into this class of drugs is at an earlier stage, but at least one clinical trial – on a CD40 agonist developed by Novartis NOVN.VX +0.09% – suggests the approach could be successful. Companies working on this approach include Agenus; Alligator Bioscience; Apexigen; AstraZeneca; Bellicum Pharmaceuticals BLCM -0.36%; Novartis; Roche; and Seattle Genetics.
Cell therapy: Tumors send out chemical signals that make it difficult for the immune system’s killer T-cells to recognize them. One strategy tries to overcome this by engineering a patient’s T-cells to recognize and attack certain molecules found on the surface of tumors.
There are two approaches to re-engineering T-cells. One approach grafts a new, tumor targeted receptor known as a “chimeric antigen receptor”, or CAR, onto the T-cell. The other, known as T-cell receptor, or TCR, gene therapy, genetically modifies an existing T-cell receptor to make it more effective at recognizing tumors.
The leading CAR-T treatments have shown promise in certain types of blood cancer, with response rates as high as 90% in otherwise difficult to treat cases of acute lymphoblastic leukemia. TCR gene therapy has shown early success in multiple myeloma patients.
Companies working on this approach include Adaptimmune Therapeutics; Amgen; Bellicum Pharmaceuticals; Celgene; Cellectis; Cellular Biomedicine; Celyad; Fortress Biotech; Intrexon;  Juno Therapeutics; Kite Pharma KITE -1.21%; MolMed; Novartis; Opus Bio; Pfizer; Sorrento Therapeutics; Theravectys, and Valeant Pharmaceuticals.
Cancer vaccines: These “train” the immune system to respond to tumors by introducing a harmless version of all or part of a tumor cell to the blood. This stimulates an immune response directed at the tumor which, in theory, strengthens the attack. But this type of immunotherapy endured several failed late-stage clinical trials.
The reasons are unclear but one theory is that, although the trained killer T-cells “know” what they are looking for, they still lack potency to get past other stealth tactics deployed by tumors. Still, the first approved cancer immunotherapy was a vaccine known as Provenge. It was approved for the treatment of prostate cancer in 2010. Newer approaches are trying to overcome this by incorporating components into the vaccine that stimulate a stronger immune response.
Companies working on this approach include Argos Therapeutics; Ascend Biopharmaceuticals; Bellicum Pharmaceuticals; Bioclones; Bio-Matrix Scientific; BioTime; DCPrime; Dendreon; ImmunoCellular Therapeutics; Kite Pharma; NeoStem; Northwest Biotherapeutics; Scancell Holdings, and Stemline Therapeutics.