Groundbreaking T-Cell Therapy to Fight Cancer Created

2024 Author: Seth Attwood | [email protected]. Last modified: 2023-12-16 15:55

The paper, published in Nature Medicine by scientists at the National Cancer Institute (NCI), describes a new type of immunotherapy that has led to the complete disappearance of tumors in a woman with metastatic breast cancer who is only a few months away.

The results show how natural tumor infiltrating lymphocytes (TIL) were extracted from a patient's tumor, grown outside the body to increase their number, and injected back into the patient to fight cancer. The patient had previously received several forms of treatment, including hormone therapy and chemotherapy, but none of them stopped the progression of the cancer. After the treatment, all of the patient's tumors disappeared, and after 22 months she is still in remission.

Scientists are enthusiastic about TIL's ability to treat a group of cancers called common epithelial cancers, which include colon, rectal, pancreas, breast and lung cancers, accounting for 90% of all cancer deaths in the United States, about 540,000 people annually, most of them from metastasis.

“As soon as these tumors spread, most people die. We don't have effective treatments for metastatic cancer,”said Steven Rosenberg, MD, PhD, head of surgery at NCI's Center for Cancer Research (CCR).

The first step in this new treatment approach is the sequencing of the tumor genome. In this patient's case, the scientists found 62 mutations in breast tumor cells. The second is to isolate TILs, which are present in 80% of epithelial cell tumors, but in tiny amounts, insufficient to destroy the tumor. They are then analyzed for their ability to recognize mutated proteins in the tumor. In the case of a patient with metastatic breast cancer, the scientists discovered TIL, which recognized four mutant proteins.

“We isolate these lymphocytes, grow them in large numbers and return them to patients. We've grown about 90 billion cells for this patient,”Rosenberg said.

During the cultivation of the TIL, the patient was also treated with the PD-1 blocking immunotherapeutic agent Keytruda in order to alter the immune system so that other immune cells would not interfere with the TIL when they were injected back into the patient.

“We include in the treatment of patients their own lymphoblasts, which are natural T cells, not genetically engineered ones. This is the most personalized treatment imaginable,”Rosenberg said.

A patient with metastatic breast cancer is not the only person successfully treated with this method. Rosenberg and colleagues have also achieved impressive results using TIL in the treatment of three more different types of metastatic cancer: colorectal, bile duct, and cervical cancer.

“These therapies are capable of treating patients with any cancer,” says Rosenberg.

Although the results are undoubtedly promising, especially because of the low level of toxicity experienced by patients compared to chemotherapy, cancer often develops resistance to treatment, and often metastases can have mutations different from the original tumor.

Is it so easy for patients to develop resistance to TIL?

“Ironically, the very mutations that caused the cancer could be the Achilles' heel that wipes out cancer. It's very important to target multiple mutations at once,”Rosenberg said.

Ironically, this is one of the advantages of many older chemotherapy drugs over new, personalized treatments. Because chemotherapy indiscriminately permeates the genome with carpet-bombing lesions, it becomes more difficult for the cancer cell to develop resistance to them. Choosing TILs that target a small number of mutated proteins in a tumor may increase the likelihood that cancer will develop resistance. More work is needed in this area, as well as techniques for studying which mutations in cancer cells are possible targets of TIL.

If major work confirms these excellent preliminary results, developing personalized patient therapy is clearly a financial and technical challenge that requires specialized laboratories and expertise. How practical is it to deliver fully personalized therapy?

“People have said that about CAR T cells as well. If you find something that works on patients, difficult or not, an engineering genius will find a way to make it work,”Rosenberg said.

And several companies are already testing TIL treatments, including Bristol-Myers Squibb and Iovance Biotherapeutics, the latter of which specifically focuses on TIL. Clinical trials of TIL are currently underway for melanoma, cervical cancer, lung cancer, and even the notoriously hard-to-treat glioblastoma and pancreatic cancer.

“This is a change in our thinking about what may be needed in the treatment of these types of cancer. A new paradigm for cancer treatment,”Rosenberg said.

It is not often that entirely new cancer treatments come into the fray with impressive results such as those shown by TIL in these examples. What is urgently needed now are the results of larger clinical trials and ongoing monitoring of patients who have been successfully treated to make sure they are not having problems.

“This is an illustrative example that once again shows us the power of immunotherapy,” said Tom Misteli, PhD, head of CCR at the NCI. "If confirmed on a larger scale, it promises to further expand the scope of this T-cell therapy to a broader spectrum of cancers."