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This aspirin tablet-sized implant made from biodegradable materials will likely activate the patient’s anti-tumor immune response, thereby producing an anti-tumor effect.

Implantable tumor vaccine

Immunotherapy, which can activate the patient’s own immune system and kill tumor cells, is probably the hottest area of ​​research and development of new drugs today. Up to now, there have been two types of cancer immunotherapy that have been approved for listing. One is a checkpoint inhibitor that can suppress the suppression of immune cell function in tumor patients, and the other is CAR-T cell therapy.

Although these therapies are very effective for some patients with cancer, there are still many obstacles in clinical applications. For example, only about one-fifth of patients can respond to checkpoint inhibitors, and cell therapy is not only a complex production process, but also The price is also very high.

To overcome these obstacles, Harvard scientists designed an implantable device that can attract immune cells into the graft after implantation into the human body, and then use the patient’s own tumor fragments to train the immunity. The cells attack the tumor cells after the immune cells are released, resulting in a persistent anti-tumor immune response.

In the first two weeks, the team reached a cooperation agreement with Novartis to allow Novartis to use this technology to develop implantable tumor vaccines. The team’s aspirin tablet-sized implants are made from biodegradable materials similar to medical suture materials and can slowly degrade over weeks to months after subcutaneous implantation.

The implants are loaded with tumor lysate and immune regulators (GM-CSF and CpG). Researchers hope that implants of this type will stimulate the immune cells of the patient and produce an immune response after transplantation. And this immune response process is also not spontaneously formed in many tumor patients.

This method does sound new and has some similarities with existing checkpoint inhibitors and CAR-T therapies, but there are many differences.

Imperfect immunotherapy

Checkpoint inhibitors can relieve the immunosuppressive state of immune cells in patients, making it easier for immune cells to recognize and kill tumor cells. The CAR-T drugs that were approved for listing last year require the extraction of T cells from patients. Through genetic modification, T cell surface express receptors that can recognize specific tumor antigens, and then the immune cells are returned to patients to produce anti-tumor effects. .

Both of these strategies are actually flawed to some extent because only about one in five patients can respond to checkpoint inhibitors. It is generally considered that this is partly because some patients cannot start an immune response against tumor cells. On the other hand, the higher response to checkpoint inhibitors in patients with a large number of tumor mutations may be due to the presence of a large number of mutated proteins, which are more likely to trigger tumor-specific immune responses. Point inhibitors provide the basis for efficacy.

For CAR-T therapy, the power of this therapy is extremely powerful if it can find a suitable target. However, if the chosen target is inappropriate, it may cause CAR-T cells to attack normal tissue cells and thus produce very serious toxicity. This is one of the major obstacles faced by CAR-T therapy in the field of solid tumors. In addition, CAR-T therapy can also cause severe CRS and neurotoxicity.

At present, although CAR-T therapy is very effective for some types of leukemia and lymphoma, it still faces many obstacles in the field of solid tumors. At least from the current progress, it is not likely that the therapy is widely used.

However, implantable cancer vaccines appear to have some advantages over these types of immunotherapy. For example, because this type of therapy is not a systemic application, the dose of immune activator can be very low, so theoretically the possibility of serious side effects is also high. relatively low.

In fact, the main purpose of this type of cancer vaccine is to trigger tumor-antigen-specific T cell responses. Therefore, it is theoretically possible to synergize with the checkpoint inhibitors and to activate the patient’s immune system against tumors at different levels.

This type of tumor vaccine can take two ways in the clinical application process. One is similar to CAR-T therapy in that specific antigens and immune cell activating factors are loaded into the implant so that the immune cells can enter the implant and then recognize the tumor antigen. In this condition, the implant can be implanted subcutaneously in the vicinity of the lymph nodes.

Another way is to separate the use of antigens and activators, and inject antigens and implants in the vicinity of the tumor, so that the immune cells activated by the implant can recognize the antigen and enter the lymph nodes to activate T cells.

This implant-based tumor vaccine is currently undergoing clinical trials at the Dana Farber Cancer Institute (ClinicalTrials.gov, NCT01753089). The cancer vaccine is actually a very promising research direction for the now very hot checkpoint inhibitor combination therapy, because tumor patients may have an immune response after the application of a tumor vaccine, and then combined with checkpoint inhibitors to release T cells. Functional inhibition may have a powerful anti-tumor effect.

There are many research directions for cancer immunotherapy, and some of these strategies may seem promising, while others may seem too indecisive, but even a theory that has sufficient theoretical basis can only be verified by clinical studies. Effectiveness to determine whether it can really benefit patients.

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