Cancer immunotherapy

Cancer treatment

Main article: Cancer treatment

2024

New immunotherapy showed 94% survival of patients with stage 3 melanoma

In early November 2024, the results of a new study were published, showing that preoperative use of the new drug vidutolimod and the PD-1 checkpoint inhibitor nivolumab ensures that tumor control is achieved in 55% of patients with stage 3 cutaneous melanoma.

The results of the study, led by researchers from the University of Pittsburgh, UPMC Hillman Cancer Center and the National Cancer Institute USA (NCI), confirm that with the new combination, the two-year relapse-free survival and metastasis-free survival in the best response group were 88% and 94%, respectively.

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Vidutolimod acts on the TLR9 receptor, a protein that plays an important role in initiating innate immune responses to external threats, including tumors. TLR9 agents are often included in drugs and vaccines due to their immunostimulating effect, but little is known about their use in combination with other cancer therapies. The new study involved 31 patients with resectable melanoma. Seven injections of vidutolimod were administered directly into tumor tissue in addition to three cycles of intravenous nivolumab administration prior to surgery. After surgery, patients continued to receive both drugs once a month for one year.

After such therapy, 55% of patients responded so well that less than 10% of viable tumor cells remained in the surgical sample, a significant predictor of long-term survival. The remaining 45% of patients either had a partial response (10-50% viable tumor cells) or no response (> 50% viable tumor cells). The researchers also used mass spectrometry to show that most patients treated with the new treatment had higher concentrations of key immunological proteins activated by the TLR9 protein^[1]

New immunotherapy provides high 10-year survival in melanoma with metastases

At the end of September 2024, scientists published long-term data from an international study, according to which the new immunotherapy ensured a high 10-year survival rate for melanoma with metastases. About half of metastatic melanoma patients treated with a combination of immune checkpoint inhibitors lived without relapse for 10 years or more.

This study involved 945 patients from 21 countries. A ten-year follow-up showed that the combination of nivolumab and ipilimumab, immunotherapies that inhibit two different immune checkpoint proteins, significantly improved treatment outcomes in a condition that had previously led to the patient's death in almost all cases. Subsequent analysis showed that in responders, the effect persisted for many years.

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News.weill.cornell.edu

The average survival in this group was about six years, and individuals without disease progression for three years were highly likely to stay alive for 10 years. At the same time, in 2011, the survival rate of patients with metastatic melanoma was only six and a half months. Crucially, no new safety concerns associated with immunotherapy were noted during the decade-long follow-up: the researchers revealed neither long-term toxicity nor a new spike in the already known effects of acute toxicity.

A team of scientists analyzed melanoma survival and overall survival over 10 years and found that patients who survive metastatic melanoma have an increased chance of dying from other causes as they age. This is an indicator of long-term treatment success -- people who responded to treatment at baseline no longer die from melanoma, the researchers said.^[1]

The first antitumor immunotherapy was started subcutaneously

On January 16, 2024, Halozyme Therapeutics announced the start of the use of Tecentrik (atezolizumab) in combination with Enhanze subcutaneous drug delivery technology based on the recombinant human hyaluronidase enzyme PH20 (rHuPH20). This is the first antitumor immunotherapy designed for subcutaneous administration. Read more here.

New immunotherapy provides 100% cancer remission in patients

On January 4, 2024, Swiss researchers from the Lausanne Federal Polytechnic School (EPFL) reported new advances in CAR-T cell therapy in the treatment of malignant tumors. Scientists have managed to achieve 100% cancer remission in patients.

CAR-T-cell therapy is a method of treating cancer patients with the help of their own immune cells, specially modified in laboratory conditions. After infusion, these prepared cells function as a tumor-targeting drug. Such immunotherapy shows good results in oncohematology, but obstacles arise with solid tumors. Modified immune cells are rapidly depleted and ultimately fail to completely destroy the cancer. Swiss researchers have proposed a way to solve the problem.

Scientists managed to achieve 100% cancer remission in patients with CAR-T therapy

Experts have created CAR-T cells that secrete the IL-10 molecule (interleukin 10), which is then taken up by modified T cells. In other words, the cell is designed to produce its own medicine to keep healthy in a hostile tumor environment. The proposed approach enhances the metabolism of CAR-T cells, which, as a result, helps to overcome the tumor.

Experiments in mice showed that even after the tumor cells are reintroduced into the body, they do not take root and show any malignancy. In other words, 100% remission is achieved. It is also noted that CAR-T cell therapy is very expensive: the cost of one treatment exceeds $500 thousand. The new approach theoretically makes it possible to radically reduce this amount due to the fact that only 5% of the traditional dose is needed for complete recovery - which means that there is no need to produce a large number of modified T cells in expensive laboratory conditions.^[2]

2023: Scientists discover 'switch' for breast cancer metastasis

On December 20, 2023, American experts from Stanford University released the results of a study in which it was possible to identify a protein called ENPP1, which functions as a "switch" for breast cancer metastases. The work could lead to new, more effective immunotherapies and help doctors better predict patients' responses to existing drugs.

Immunotherapy such as pembrolizumab (Keytruda) works by blocking the immunosuppressive interaction between a cancer cell and a T cell, a type of immune cell. However, to achieve the desired result, T cells must penetrate the tumor. So-called "hot" tumors, in particular melanoma and some types of lung cancer, are treatable with immunotherapy because T cells infiltrate the neoplasm. However, many other tumor types, including breast and pancreatic cancers, are considered "cold" because T cell penetration is difficult.

It was possible to identify a protein called ENPP1, which serves as a "switch" for breast cancer metastases

In the course of the work done, the researchers sought to convert "cold" tumors into "hot" tumors for subsequent treatment through immunotherapy. Experts have studied the cGAMP molecule, which is produced when cells become cancerous and their DNA is damaged. cGAMP has been found to activate the immune response through the STING pathway, which helps to "warm up" the tumor. At the same time, the ENPP1 protein prevents this process, which is why malignant formations remain "cold."

It is noted that the ENPP1 protein is produced by cancer cells, and healthy ones - inside and around the tumor. At the same time, the researchers showed that high levels of ENPP1 in patients are associated with resistance to immunotherapy and the formation of metastases. So, scientists say, ENPP1 is crucial in metastases, not just primary tumors. Moreover, this protein should be searched for in healthy cells, and not only in cancer.^[3]

2021: New cancer treatment created combining chemotherapy and immunotherapy

In mid-October 2021, researchers from Massachusetts Institute of Technology discovered new ways to trigger the immune system and attack tumors. The method consists in immunotherapy, this strategy involves stimulating the patient's own immune system to destroy tumor cells, but this approach works only for a few species. cancer

For the new approach, tumor cells are treated with chemotherapy drugs and returned to the tumor. Cancer cells are damaged when drugs that activate cancer T lymphocyte cells are delivered, apparently acting as distress signals to prompt T cells to start an attack. As Professor of Medical Sciences Michael Jaffe noted, if you create cells that have damage in DNA but are not killed, then the rest of the cells can give them signals for emergency awakening if they are alive under certain conditions.

New cancer treatment combining chemotherapy and immunotherapy unveiled

In a mouse study, the scientists found that this treatment could completely eliminate tumors in nearly half of the mice. Professor Underwood-Prescott and Deputy Director of the Koch Institute, Michael Jaffe and Darrell Irvine, appointed to the MIT Department of Biotechnology and Materials Science and Engineering, on October 19, 2021, scientifically signal this study. One class of drugs used in cancer immunotherapy is checkpoint block inhibitors, which take the brakes off T cells exhausted and unable to attack tumors. These drugs have been successful in treating some cancers, but they are ineffective against many other cancers.

Darrell Irvine and colleagues hope that chemotherapy will help stimulate the immune system to kill tumor cells and improve the effectiveness of these drugs by combining them with cytotoxic chemotherapy drugs. This approach is based on a phenomenon known as immunogenic cell death. In this phenomenon, dead or dying tumor cells send signals that attract the attention of the immune system. For October 20, 2021, several clinical trials are underway that combine chemotherapeutic and immunotherapeutic agents, but little is known about how to best combine the two treatments.

The MIT (MIT) team began by treating cancer cells with several different chemotherapeutic agents at different doses and 24 hours after treatment, the researchers added dendritic cells to each sample and, 24 hours later, T cells. They then measured how well T cells were able to kill cancer cells. Surprisingly, they found that most chemotherapeutic drugs were not very useful. And those that helped worked best in small doses without killing many cells. Over time, the researchers understood why this was happening. Non-dead tumor cells stimulated the immune system. Instead, the key factor was cells damaged by chemotherapy but still alive. The drugs that turned out to be most effective in this approach cause DNA damage. The researchers found that DNA damage in tumor cells activates cellular pathways that respond to stress. These pathways send distress signals, thereby stimulating T cells to act and destroying not only damaged cells, but also nearby tumor cells.^[4]

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