Don't panic if immunotherapy fails! A new combination therapy is about to emerge, or save 80% of cancer patients

▎ WuXi AppTec content team editor In cancer treatment, the efficiency of killing tumors can be better increased by combining different therapies.
For example, under suitable conditions, chemotherapy is usually used together with immune checkpoint inhibitors
.

However, many chemotherapeutic drugs will attack all cells indiscriminately, and even cause bone marrow suppression, which will greatly reduce the effectiveness of immunotherapy
.

Is there a better combination? At the "Molecular Targets and Cancer Therapies" conference jointly organized by the European Organization for Cancer Research and Therapy (EORTC), the National Cancer Institute (NCI) and the American Society for Cancer Research (AACR), from Cybrexa Therapeutics, a tumor-targeted therapy research and development company Dr.
Sophia Gayle introduced a new peptide-conjugated drug CBX-12
.

The most unique feature of CBX-12 is that it can specifically deliver a cytotoxic chemical drug exatecan to a low pH environment
.

This is mainly achieved by a polypeptide that undergoes conformational changes in an acidic environment
.

This way of presentation can make the drug only work in the tumor microenvironment with a very low pH, and no longer threaten normal cells and tissues
.

▲How CBX-12 works (picture source: reference [2]) "The novelty of CBX-12 lies in its acidic targeting ability, which is a feature of almost all types of tumors," said Dr.
Gayle, "therefore Such a drug can be used in a wide range of cancer patients
.

"Many chemical drugs now attack normal cells indiscriminately, while some antibody drugs require patients to express high levels of antigen targets, and CBX-12 can overcome their encounters.
Difficulties
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Image source: 123RF In mouse experiments, mice treated with CBX-12 did not suffer from bone marrow suppression.
The research team speculated that the use of CBX-12 in combination with immunotherapy would become a potential combined anti-cancer therapy
.

Dr.
Gayle and colleagues selected a group of colorectal cancer mice, and first gave them anti-PD-1 and anti-CTLA4 immune checkpoint inhibitors, and then supplemented with CBX-12 treatment
.

The results showed that compared with mice using immunotherapy alone, mice using combination therapy slowed their tumor growth significantly.
The combination of CBX-12 and PD-1 can increase the tumor growth delay time by 4 times.
The survival rate of mice has also increased
.

However, mice whose tumors completely regressed under the combination therapy can acquire long-term immune memory, which can resist subsequent tumor growth injected into the body
.

Even injecting CBX-12-treated tumor cells into mice alone can also cause a strong anti-tumor immune response, which means that CBX-12 can cause an immunogenic cell death process
.

"Our research shows that the combination of CBX-12 and immune checkpoint inhibitors may have an effect on tumors for which immunotherapy is usually ineffective," said Dr.
Gayle.
This means that 80% of those who do not respond to immunosuppressants alone may not respond.
Patients can benefit from it
.

At present, the research team is advancing related clinical trials to determine the safety and appropriate dosage of the therapy
.

Perhaps in the near future, this combination therapy will free most patients from cancer
.

Reference: [1] A peptide-drug conjugate that targets the acidic environment of cancer cells may improve the efficacy of immunotherapy.
Retrieved OCT.
11, 2021 from https://medicalxpress.
com/news/2021-10-peptide-drug -conjugate-acidic-environment-cancer.
html[2]Gayle S, Aiello R, Leelatian N, et al.
Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity[J ].
NAR Cancer, 2021, 3(2): zcab021.