Recent FDA Approval Opens New Possibilities for CAR T-cell Therapies

Published on in Children's Doctor

Looking back, 2017 was the year that gene therapy and immunotherapy have really come into their own, especially for pediatric patients.

You may have heard about CAR T-cell therapy, which is an engineered cell therapy/immunotherapy for cancer that works especially well in blood cancers like leukemia. Our Cancer Immunotherapy Program team at Children’s Hospital of Philadelphia has been at the forefront of developing this therapy. The idea is to take T cells from patients, genetically engineer them into cancer-killing CAR T cells, then give them back to the patients.

The concept has been around for a while, but a CHOP-University of Pennsylvania collaboration showed for the first time how powerful this cell therapy could be, with the first adult and the first pediatric patients going into remission despite having a disease that was completely out of control.

This has led to multicenter trials and a global registration trial of this therapy, called CTL019 or CART19 by CHOP and Kymriah by Novartis, which has licensed the treatment and is developing it commercially. Our group at CHOP led these trials globally.

Fast forward 5 years from our first patient, and where are we? We have treated more than 200 patients with CAR T cells at CHOP, making us one of if not the busiest cell therapy center in the world. We saw Food and Drug Administration (FDA) approval of this therapy, the first gene therapy and the first engineered cell therapy ever approved by the FDA.

It’s hard to get drug companies interested in approving drugs for kids, and it’s nearly unheard of for a first-in-class therapy to be approved first in pediatrics, but Kymriah (tisagenlecluecel) was approved August 30, 2017, by the FDA for the treatment of pediatric and young adult patients (up to 25 years of age) with B-cell acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. This approval has opened the door to a whole new field of medicine.

Five years and counting

CHOP has been at the forefront of developing this therapy. Our first ALL patient has been in remission for more than 5 years without further treatment, including no need for bone marrow transplant, the previous standard of care for relapsed ALL. Since 2012, the Cancer Immunotherapy Program at CHOP has treated more leukemia patients using CAR T cells than any other hospital, allowing us to develop the most experienced team of cell therapy experts — oncologists, intensivists, nurses, and nurse practitioners. Taking it forward post-FDA approval, we have successfully treated the first patient with the FDA-approved product.

We’ve been innovating since day one. At the time of that first infusion, our team discovered the importance of interleukin-6 (IL-6) to cytokine release syndrome (CRS), the major toxicity of CAR T cells. In our first patient, we used a drug that blocks IL-6, and that drug was approved by the FDA for CRS at the same time as this CAR T-cell therapy. This discovery allowed us to develop the toxicity management protocols that have allowed safe use of multiple CAR T-cell therapies, without which FDA approval would not have been possible.

New treatments are under development. We are developing alternative targets for ALL other than CD19, which is the target for CTL019. We are testing a second-generation version of the recently approved therapy, to see if it might work better or stay in the body longer. Working with the leukemia group at CHOP, we are hoping to initiate clinical trials in a different kind of leukemia, specifically acute myelogenous leukemia (AML), going after new targets in that disease.

Solid tumors next challenge

Looking beyond that, we are faced with the challenge of trying to make this cell therapy work as well in solid tumors as it does in blood cancers. This is a big challenge, and the work of the next 3 to 5 years. New technologies that will enable multiple genetic changes to be made in T cells, such as CRISPR gene editing, will be part of therapies in 2020 and beyond. We can see real possibilities for gene-modified cell therapies for genetic disease like sickle cell disease.

The excitement around gene therapy at CHOP has moved beyond cancer with the very recent approval of Luxturna; more on that to come! It’s worth noting that the first 3 gene therapies ever approved were approved in 2017, and 2 of them were developed at CHOP. It’s an amazing time for translational science and for the patients we treat.

Learn about the latest developments in CAR T-cell therapy on June 7 at a one-day Continuing Medical Education conference, Advances in Cellular Immunotherapy and Stem Cell Transplantation.

Referral information

To refer a patient to the Cancer Center at Children’s Hospital of Philadelphia, call 267-426-0762.

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New Patients, Referrals and 2nd Opinions

Referring a Patient

Here’s what you can expect after contacting the Cancer Immunotherapy Program.

Torie CART

Cancer Immunotherapy Studies

The Cancer Immunotherapy Program has several clinical trials available to qualified patients.

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Torie CART

Cancer Immunotherapy Studies

The Cancer Immunotherapy Program has several clinical trials available to qualified patients.


CAR T-cell Therapy

In CAR T-cell therapy, immune cells called T cells are genetically modified to recognize cancerous B cells.

Referring a Patient

Here’s what you can expect after contacting the Cancer Immunotherapy Program.