Lymphocyte Adoptive Therapy

Lymphocyte adoptive therapy is a form of immunotherapy that uses a patient’s own immune cells to fight cancer. These cells are collected, grown to large numbers in a laboratory, and then returned to the patient to help destroy tumors.

Table of contents

• What is Lymphocyte Adoptive Therapy?
• Other Names for This Treatment
• Main Types of Treatment
• How the Treatment Works
• Which Cancers Can Be Treated

adoptive cell therapy, adoptive immunotherapy, immune cell therapy, T-cell transfer therapy, cellular immunotherapy

What is Lymphocyte Adoptive Therapy?

Lymphocyte adoptive therapy is a treatment that harnesses the power of a patient’s own immune system to fight cancer. This approach uses special white blood cells called lymphocytes, which are a type of immune cell naturally designed to recognize and kill harmful invaders in the body, including cancer cells.^[2]

The treatment works by collecting immune cells from a patient, growing them to very large numbers in a laboratory setting, and then giving them back to the patient through an injection into a vein. The goal is to provide the body with enough strong, cancer-fighting cells to overcome the tumor.^[2]

This type of therapy represents a major advancement in cancer treatment. Unlike traditional treatments that directly attack cancer cells with drugs or radiation, lymphocyte adoptive therapy strengthens the body’s own immune response. It is part of a broader category of treatments called immunotherapy, which helps the immune system work better against cancer.^[4]

Other Names for This Treatment

Doctors and researchers may use several different terms to describe this treatment approach. It is commonly called adoptive cell therapy or ACT. Other names include adoptive immunotherapy, immune cell therapy, and T-cell transfer therapy.^[2][4]

All these terms refer to the same basic idea: taking immune cells from a patient, preparing them in a laboratory to fight cancer more effectively, and then returning them to the patient’s body.

Main Types of Treatment

There are three main types of lymphocyte adoptive therapy, each using a slightly different approach to help immune cells recognize and destroy cancer.^[2][4]

Tumor-Infiltrating Lymphocyte Therapy

Tumor-infiltrating lymphocyte therapy, often called TIL therapy, uses immune cells that are already inside or near a patient’s tumor. These cells have already shown they can recognize the cancer, but there may not be enough of them to destroy the tumor completely.^[2]

To perform this treatment, doctors surgically remove a piece of the patient’s tumor and isolate the lymphocytes from it. In the laboratory, scientists test these cells to find the ones that respond best to the tumor. Then, these selected cells are treated with special substances that make them multiply rapidly to create very large numbers. After growing for several weeks, millions or even billions of these cancer-fighting cells are given back to the patient.^[2][4]

Before receiving the cells back, patients typically undergo chemotherapy and sometimes radiation therapy to reduce their other immune cells. This step helps the returned TIL cells work more effectively.^[2]

Engineered T Cell Receptor Therapy

Engineered T cell receptor therapy, or TCR therapy, is used when patients do not have enough lymphocytes that naturally recognize their tumors. In this approach, doctors collect regular immune cells from the patient’s blood and then modify them in the laboratory.^[4]

Scientists insert new genes into these cells that give them a special T cell receptor. This receptor acts like a targeting system that allows the cells to find and attach to specific markers on cancer cells. The modified cells are then grown to large numbers and returned to the patient.^[3]

TCR therapy can only work when cancer cells display their markers in a specific way, bound to a molecule called major histocompatibility complex or MHC. This is how the immune system normally recognizes cells in the body.^[4]

CAR T Cell Therapy

CAR T cell therapy is similar to TCR therapy but uses a different kind of modified receptor. CAR stands for chimeric antigen receptor. This synthetic receptor is created in the laboratory and combines parts from different sources to create a powerful cancer-fighting tool.^[2]

The key advantage of CAR T cells is that they can recognize and attack cancer cells even when the cancer markers are not presented through MHC. This means they can target more cancer cells. However, CAR T cells can only recognize markers that appear naturally on the cell surface, which limits the number of potential targets compared to TCR therapy.^[4]

How the Treatment Works

The process of lymphocyte adoptive therapy takes several weeks from start to finish. First, doctors collect immune cells from the patient. For TIL therapy, this requires surgery to remove part of the tumor. For TCR and CAR T cell therapy, cells are typically collected from the blood.^[2]

Once collected, the cells are sent to a specialized laboratory where they are processed. For TIL therapy, the cells that best recognize the tumor are selected and multiplied. For TCR and CAR T cell therapy, the cells are genetically modified to add new cancer-targeting abilities. Growing the cells to sufficient numbers can take anywhere from 2 to 8 weeks.^[2]

Before the cells are returned to the patient, most people receive chemotherapy to reduce their existing immune cells. This lymphodepleting treatment helps create space and resources for the new cells to grow and function effectively.^[2][3]

The modified or expanded cells are then given back to the patient through a needle inserted into a vein, similar to a blood transfusion. After the infusion, patients receiving TIL therapy also typically receive a medication called interleukin-2 or IL-2, which helps the transferred cells survive and multiply in the body.^[3]

The transferred cells travel through the bloodstream to find and attack cancer cells wherever they are in the body. Large numbers of these specialized cells can overcome barriers that prevent the immune system from controlling the tumor, such as signals from the cancer that suppress immune activity.^[2]

Which Cancers Can Be Treated

Different types of lymphocyte adoptive therapy have been approved or are being studied for different cancers. The U.S. Food and Drug Administration has approved one TIL therapy called lifileucel (brand name Amtagvi) specifically for treating melanoma, a type of skin cancer. This was the first cell therapy ever approved for a solid tumor.^[2]

TIL therapy has also shown promising results in research studies for other solid tumors, including cervical squamous cell carcinoma and cholangiocarcinoma, but these uses are still considered experimental.^[2]

CAR T cell therapy has been particularly successful for blood cancers. Six different CAR T cell therapies have received FDA approval for treating various types of leukemia and lymphoma. These approved therapies include axicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), ciltacabtagene autoleucel (Carvykti), idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), and tisagenlecleucel (Kymriah).^[2]

Researchers are also studying CAR T cell therapy for solid tumors such as breast cancer and brain cancer, but these applications remain experimental.^[2]

Clinical studies have shown that adoptive cell therapy can produce significant responses in patients. For example, approximately 50% of patients with metastatic melanoma who have not responded to other treatments experience tumor shrinkage with TIL therapy. Some patients achieve complete responses where the cancer disappears entirely, and these responses can be long-lasting.^[3][5]