CAR T cell therapy- Reprogramming T cells to fight cancer

CAR T cell therapy- Reprogramming T cells to fight cancer

Cancer has been the leading cause of deaths across the globe. Limited efficacy of conventional treatments such as chemotherapy, and a higher relapse rate poses a major challenge in cancer treatment and demands the development of novel therapies such as CAR T-cell therapy in management of cancer.

After several decades of painstaking research, the development of immunotherapy has helped to reach a tipping point in the field of cancer. Among immunotherapy, Chimeric antigen receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for cancer.

CAR T-cell therapy is a fairly novel therapy which involves modifications in your immune cells to treat cancer. In cancer research studies, this cancer treatment has shown promising efficacy in management of blood cancers.

But before undergoing this therapy, one must wonder: what exactly is CAR T-cell therapy? Who should consider it? What is the procedure? What are the recovery rates? And what are the possible side effects?

So, Let’s start with the basics of CAR T cell therapies including its mechanism of action, efficacy, safety and the recovery rates.

What exactly is CAR T-cell therapy?

Our immune system consists of two major types of white blood cells: B and T cells. Among these cells, T cells are responsible for recognizing and destroying cancer cells but sometimes these cells miss the cancer cells as they look too much like abnormal cells.

Also, T cells lack the right receptor to bind to cancer or tumor cells as these abnormal cells have certain receptors on their surface. Here comes the CAR T-cell therapy which reprograms the immune system, so that T cells can better recognise cancer cells and destroy them.

Scientifically speaking, CAR T-cell therapy involves genetic modifications in a patient’s T cells and developing an antibody-like protein CAR on their surface. These genetically engineered T cells are able to easily recognise cancerous cells, thus destroying them.

Who is eligible to receive CAR T-cell therapy ?

A person who has been diagnosed with blood cancer or has already received two lines of treatment for blood cancers is eligible to receive CAR T-cell therapy. Various types of cancer for which CAR T-cell therapy is approved are:

  • Relapsed or refractory acute lymphoblastic leukemia up to age 25.
  • Relapsed or refractory multiple myeloma
  • Relapsed or refractory follicular lymphoma
  • Aggressive, relapsed or refractory non-Hodgkin lymphoma including diffuse large B cell lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, transformed follicular lymphoma, mantle cell lymphoma
Which CAR T-cell therapy approved for treatment?

Currently, CAR T-cell therapy has been approved by the Food and Drug administration (FDA) for management of hematological or blood cancers. Some of the FDA approved CAR T-cell therapy are:

  • Axicabtagene ciloleucel for certain types of relapsed/refractory large B-cell lymphoma and relapsed or refractory follicular lymphoma (FL).
  • Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma (MCL).
  • Lisocabtagene maraleucel for certain types of large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
  • Tisagenlecleucel for certain types of relapsed/refractory large B-cell lymphoma.
  • Idecabtagene vicleucel for patients with relapsed or refractory multiple myeloma.
  • Tocilizumab for pediatric ( ≥2 years of age) and adult patients with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS).

Although CAR T-cell therapy has achieved success in hematological cancer, its potential to treat solid tumors or non hematological tumors including cancers of the cervix, mouth, throat and lung cancer is under investigation.

What is the procedure or process of CAR T-cell treatment?

The CAR T-cell therapy is carried out in five steps:

  1. Blood is collected from the patient. T-cells are separated from the blood using a special machine and then returned back to the patient. This process is called leukapheresis and takes about 4-5 hours to complete. It is a painless procedure and sometimes may lead to fainting, redness, discomfort, muscle spasms and anemia.
  2. These T cells are then sent to the lab and CAR-coding viral DNA is incorporated in T cells from an inactivated virus. These cells are now reprogrammed and contain CAR receptors at the surface of these cells.
  3. These new CAR T-cells are grown and multiplied in the lab and it usually takes a few weeks.
  4. New CAR T-cells are injected back into the patient, and now these cells are able to recognise, attack and destroy cancer cells. It will take about 30 minutes to 1 hour.
  5. After CAR T-cells infusion, the patient will be kept under observation and closely monitored for about 2 weeks for risk of complications. Either he/she can stay in the hospital or can stay nearby which should be within an hour’s drive from the treatment center or cancer center for up to 28 days after the treatment.
What are the advantages and response rates of CAR T-cell therapy?

The major advantage of this therapy is that the patient only requires one infusion which only takes 2 weeks compared to other treatments which require 6 months. This therapy benefits last for several years, thus the chances of cancer relapse are low. Also, the recovery rates are faster than stem cell transplants in which aggressive chemotherapy is used.

Initial response rates and efficacy of CAR T-cell therapy particularly in leukemia patients have been encouraging. It is the most potential treatment with successful treatment outcomes. Clinical trials have indicated about 80% patients receiving CAR T-cell therapy have achieved remission.

What are the possible side effects of CAR T-cell therapy?

Besides good treatment outcomes and better prognosis, approximately 40-60% patients reported some unusual and mild adverse events. The most common side effects are:

  • Allergic reactions with fever, chills and increased risk of infections.
  • Cytokine release syndrome characterized by flu-like symptoms such as fever, nausea, headache, fatigue and body pain. It may occur after the 2nd or 3rd day of infusion and last for five to seven days.
  • CAR T-cell-related encephalopathy syndrome characterized by neurological symptoms such as confusion, seizures, short-term memory loss, depression and speech changes for some days. It appears around the 5th day of infusion and lasts for two and four days.
  • High uric acid levels in the blood, due to breaking down of cancer cells.
Conclusion

Taken together, CAR T-cell therapy has emerged as an innovation in cancer management. It is offering hope to people who have previously been given only about six months to live. With these advanced therapies, the future looks much brighter for cancer patients.

Right now, this therapy can target only CD-19 molecules on cancer cells. Research needs to look for future CAR T-cell therapy which can target multiple molecules on cancer cells and ways to reduce side effects and toxicity associated with this type of therapy.

Also explore the role of complementary therapies to reduce pain and other symptoms of cancer.

Frequently asked questions (FAQs)

Q. Is CAR T-cell therapy available in India?

Ans. CAR T-Cell Therapy in India is under development and is expected to be available from next year.

Q. Is CAR T-cell therapy expensive?

Ans. As CAR T-cell therapy is a specialized and personalized treatment, the manufacturing and treatment costs are very high.

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