Cellular Immunotherapy

Cellular immunotherapy is an innovative cancer treatment approach. What is immunotherapy? Immunotherapy is a treatment that harnesses the power of the body’s immune system to target and destroy tumor cells.

A guide to cancer immunotherapy: from T-cell basic science to clinical practice

People often ask why the body's immune system doesn't recognize cancerous cells as harmful invaders and destroy them, much like viruses and bacteria. Actually, it does.

The eliminating phase

In the early stages of a malignancy, the immune cells are often able to find rogue cancer cells as they develop. During that time, which is known as the “eliminating phase,” the immune system remains in control of the tumor by destroying individual cancer cells one at a time.

The state of equilibrium

As the tumor progresses, its growth rate may eventually catch up to the activity rate of the immune system, leading to a state of balance. At that point, the immune cells are still able to keep up with and eliminate the growing cancer cells, but the immune cells must work harder to do so. In some cases, the immune system can keep a growing tumor in check for several years.

The escape phase

Approximately a decade ago, a group of researchers made a groundbreaking discovery: They found that certain types of cancer can effectively “put the brakes on” the body’s immune system. More specifically, those cancer cells evolve and undergo genetic changes that help them hide from the immune cells. During that time, which is known as the “escape phase,” the cancer cells continually come up with creative ways to avoid the immune system and escape its detection. Ultimately, the growth rate of the cancer cells surpasses the activity rate of the immune cells.

Detection and evasion

Prior to the escape phase, the immune cells are able to recognize the cancer as a harmful invader by closely inspecting the molecules found on the surface of the tumor cells. During the escape phase, however, the “red flag” molecules that alert the immune cells to the danger of the cancer are lost, allowing the cancer cells to slip by the immune system and go unnoticed. Some cancer cells also produce molecules that create a hostile environment for the immune cells, which renders the immune cells ineffective.

The advent of immunotherapy

Through extensive research, scientists have discovered ways to reverse the evasive tactics of stealthy cancer cells and prevent the immune cells from falling for them. One example is the development of a unique class of drugs known as immune checkpoint therapy, which can effectively “take the brakes off” the immune system so that it can once again fight the cancer. Checkpoint inhibitors are now routinely used to treat several types of cancer, including lung cancer, kidney cancer and melanoma. As research continues, more immunotherapies are being developed to bolster the immune system and help it get the better of cancer cells.

Immunotherapy vs. chemotherapy

Is immunotherapy chemo? No. Although both immunotherapy and chemotherapy can be used to fight cancer, they do so in markedly different ways. Chemotherapy is a reactive approach that uses powerful drugs that are administered orally or intravenously. The drugs then enter the bloodstream and circulate throughout the body to target and destroy widespread cancer cells. Immunotherapy is a proactive approach that involves stimulating the immune system to seek out and attack cancer cells—and to continue to do so even after the treatment has ended. Another difference between chemotherapy and immunotherapy is that the effects of chemo may become apparent right away as the drugs immediately shrink tumors and kill cancer cells, while the effects of immunotherapy tend to occur over a longer period of time. 

What is immunotherapy for cancer?

Moffitt Cancer Center currently offers several types of immunotherapy for cancer treatment, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR) gene transfers and tumor-infiltrating lymphocyte (TIL) therapy. Our dedicated research team is continually investigating promising new immunotherapies, which are helping to transform the treatment landscape for many current and future cancer patients.

Types of immunotherapy for cancer

How does immunotherapy work? Well, that depends on the type of immunotherapy being implemented. Cell therapies can be used to treat cancer in several ways:

CAR T-cell therapy

CAR T-cell therapy is a highly tailored treatment that capitalizes on the infection-fighting ability of certain white blood cells known as T-cells, which normally help the immune system fend off harmful invaders such as viruses, bacteria and cancer. The goal of T-cell immunotherapy is to modify the patient’s T-cells so that they are better equipped to recognize the patient’s cancer cells as invaders. The treatment involves the placement of a specific protein (CAR) on the surface of the patient’s T-cells, essentially creating a “living drug.” While CAR T-cell therapy is similar to monoclonal antibodies immunotherapy, the former is much more engineered than the latter. And unlike passive immunotherapy, CAR T-cell therapy works as an active medication.

How is immunotherapy administered? Healthy T-cells are derived from the patient’s blood through a process known as leukapheresis, during which the blood passes through a machine that collects a high concentration of white blood cells and returns the red blood cells, platelets and plasma to the patient’s bloodstream. The T-cells are then genetically modified in a lab to add the CAR to their surface, after which the CAR T-cells are duplicated and returned to the patient’s bloodstream via intravenous infusion. As the CAR T-cells circulate throughout the patient’s body, they will be guided by the engineered chimeric antigen receptors to recognize cancer cells as harmful invaders. The cell receptors will attach to certain proteins found on the surface of the targeted cells, then destroy those cells.

Who qualifies for immunotherapy? Currently, CAR T-cell therapy is approved by the U.S. Food and Drug Administration (FDA) for treating certain blood cancers, including:

• Diffuse large B-cell lymphoma (DLBCL)
• Follicular lymphoma
• Mantle cell lymphoma
• Multiple myeloma
• Chronic lymphocytic leukemia
• B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients up to age 25

Scientists continue to explore the potential of CAR T immunotherapy for treating other blood cancers and solid tumors.

TCR gene transfers

In recent years, adoptive cell therapy with engineered T-cells—most notably, CAR T-cell therapy—has provided new immunotherapy treatment options for certain cancer patients. Along those same lines, scientists are now evaluating opportunities to utilize TCR technology to target cancer antigens that cannot be reached with CAR technology. Specifically, TCR therapy is a gene immunotherapy technique in which the patient’s T-cells are genetically engineered to express a specific TCR that targets a particular antigen.

A group of proteins found on the surface of T-cells, TCRs attach to certain antigens found on abnormal cells, such as cancer cells. The T-cell receptors then attack the abnormal cells and thus help the immune system fight off the pathogen. Through TCR gene transfers, which involve inserting an exogenous TCR into T-cells, the T-cells can be redirected to target specific antigens found on the surface of a tumor and thus help eliminate cancer cells.

Who qualifies for immunotherapy? In clinical trials, TCR gene transfers have shown promise in treating:

• Lung cancer
• Sarcomas
• Multiple myeloma

As scientists continue to develop and refine gene engineering techniques, the potential of adoptive T-cell therapy for cancer is dramatically shifting, making this innovative treatment option accessible to more patients with different tumor types.

TIL therapy

Currently available in clinical trials, TIL therapy is an innovative cancer treatment designed to capitalize on the fact that some tumors contain TILs, a type of immune cells that can recognize and kill cancer cells. After the patient’s tumor is biopsied or removed, TILs are collected from a tissue specimen and treated in a lab with interleukin-2 (IL-2), a protein that causes the cells to rapidly reproduce. A large army of cancer-fighting TILs is then intravenously infused into the patient’s bloodstream. The TILs can then reach and destroy cancer cells as they circulate throughout the patient’s body.

Because TILs are derived directly from the patient’s tumor, they have the inherent ability to identify many unique targets on cancerous cells, so they don’t have to be genetically engineered to recognize the tumor. This is a key advantage because stealthy cancer cells are often able to evade the immune system by effectively “hiding” one target at a time. Another potential advantage of TIL therapy is that it may be long-lasting; in some cases, the TILs continue to patrol the patient’s body for several years after a single infusion.

Who qualifies for immunotherapy? TIL therapy can be used to treat:

• Metastatic melanoma
• Squamous cell carcinoma of the head and neck
• Breast cancer
• Cervical squamous cell carcinoma and other gynecological cancers
• Cholangiocarcinoma

Through extensive studies now underway, researchers are evaluating the potential of TIL therapy for other types of cancer as well.

What is the success rate of immunotherapy?

Immunotherapy is a relatively new type of precision medicine. Most of the therapies approved by the U.S. Food & Drug Administration (FDA) have been in use for less than a decade. The results achieved to date show great promise, and as scientists continue to study how cellular immunotherapies change cancer patients’ prospects, the use of emerging cancer immunotherapies is expected to increase substantially in coming years.

While immunotherapy works well for certain patients, it is important to keep in mind that it is not a cure for every type of cancer, nor is it the best treatment for every patient.

Cellular immunotherapy at Moffitt Cancer Center

Cellular immunotherapy is an active area of research at Moffitt, and one we firmly believe represents a new era in cancer treatment. Our renowned scientists and clinicians are continually studying signs immunotherapy is working and exploring new ways to use these advanced therapies with the goal to one day find a cure. For instance, recent studies suggest that low-dose immunotherapy could be just as efficacious as the currently recommended doses, which could potentially reduce the overall cost of the treatment. We believe this finding is significant because it could ultimately make this potentially life-saving treatment accessible to more patients.

Additionally, in a recent article published in the Journal for ImmunoTherapy of Cancer, Moffitt researchers show that PET/CT images can be used to measure the levels of the PD-L1 biomarker of non-small cell lung cancer (NSCLC) patients in a non-invasive manner. This valuable information can be used to predict a patient's response to checkpoint inhibitor immunotherapy.

These are just a few examples that illustrate why Moffitt is a recognized leader in cancer immunology and immunotherapy research. Through our robust clinical trials program, many of our patients have unique opportunities to be among the first to benefit from groundbreaking options that are not yet available in other settings. Our multispecialty team is committed to providing outstanding clinical care for those who receive immunotherapy cancer treatment. We also provide supportive care for those who experience side effects such as cytokine release syndrome, which can result from an overly robust immune response to treatment.

If you would like to learn more about cellular immunotherapy, you can request an appointment with a specialist at Moffitt Cancer Center by calling 1-888-663-3488 or completing a new patient registration form online. We will connect you with an expert who can further explain the immunotherapy definition as well as the benefits of immunotherapy vs. chemo and targeted therapy vs. immunotherapy. We will begin planning your personalized treatment before you even step through our doors. As Florida’s top cancer hospital, we are transforming the model by providing our patients with the benefit of tomorrow’s treatments today.

References:

National Cancer Institute: CAR T cells
National Cancer Institute: TIL Therapy
PubMed: T-cell receptor gene transfer for the treatment of leukemia and other tumors
National Cancer Institute: T Cell Transfer Therapy