Developments in Cellular Therapy

The field of immunotherapy, in which researchers try to harness the immune system to combat illness, is changing the way we think about—and treat—diseased tissue. Frost & Sullivan believes the following companies show promise in their capabilities to not only elevate the field of cellular therapy, but also change the way cancer and autoimmune disorders are treated.

The field of immunotherapy, in which researchers try to harness the immune system to combat illness, is changing the way we think about—and treat—diseased tissue. Some approaches rely on stimulating nerves to induce an immune response; others attempt to limit the activity of immune cells. Still others, such as chimeric antigen receptor (CAR) T-cell and allogenic therapies, use genetic engineering to tailor treatment to a specific patient and/or disease. Many of these approaches have been successful, but downsides range from clinical uncertainty in human subjects to high cost and lengthy production or treatment times.

Frost & Sullivan believes the following companies show promise in their capabilities to not only elevate the field of cellular therapy, but also change the way cancer and autoimmune disorders are treated.

Inflammation Inhibition with CAR T-Cell Therapy

Inflammatory disorders lack a robust therapeutic product; most therapies provide only symptomatic relief. The development of novel CARs could provide patients with a respite.

CARs are genetically engineered to combat disease processes. The artificial receptors are grafted onto naturally occurring T cells to inhibit unwanted inflammatory response and ameliorate the disease.

TxCell is a French biotechnology company that is developing CAR T-cell immunotherapies for inflammatory and autoimmune diseases. Ovasave, the first pharmaceutical from its antigen-specific regulatory T cell (ASTrla) technology platform, activates T cells to create a cytotoxic environment by releasing local immune suppression factors. Traditional processes of removing a patient’s T cells and genetically altering them in a lab generally take between 17 and 29 days. The engineered cells are then infused back into the patient. TxCell’s new method can isolate non-engineered T cells and reduce overall production time by nearly 50%. In September 2017, TxCell confirmed it had fully optimized the ASTrIA manufacturing process.

Using Allogenic Therapy to Treat Cancer

Celyad, a Belgian biopharmaceutical company, is developing allogenic cellular therapies using natural killer receptor-2 (NKR-2) CYAD-01. Its differences from traditional CAR T-cell therapies are the CAR design and the receptor-to-antigen adhesion. CYAD-01 T cells can target more than one tumor antigen. The therapy enables the NKR to adhere to the NKG2D ligand, essentially killing the tumor cell. NKRs adhere to more than 8 ligand—80% of the ligand expressions present in tumors.

A Phase 1 single-dose escalation trial on patients suffering from acute myeloid leukemia (AML) and multiple myeloma was completed in Europe in 2016. The NKR-2 therapy was developed using NKRs that were transduced on T lymphocytes. In October 2017, Celyad reported the first- ever morphologic complete response with gene-engineered T cells without pre-conditioning chemotherapy for a patient with relapsed refractory AML.

The U.S. Food and Drug Administration has authorized the initiation of an open-label Phase 1b study to test the therapy’s safety and clinical efficacy in five solid tumors and two hematological cancers.

Allogenic Therapy in a Fraction of the Time

French biopharmaceutical company Cellectis is developing allogenic immunotherapies specifically for treating AML and blastic plasmacytoid dendritic cell neoplasm using its proprietary gene editing technology, transcription activated-like effector nucleases (TALEN). Although TALEN is more expensive than CRISPR technology, its ability to apply a wide range of specificity to the engineered T-cell receptors has had an important impact in the development of allogeneic CAR T-cell therapies.

Cell extraction from patients with insufficient T cells is particularly difficult. Alternate methods have been suggested in which cells are taken from a patient earlier in the treatment process; however, this is a logistical nightmare. The TALEN technology produces universal, off-the-shelf CAR T-cell (UCART) therapies capable of large-scale manufacturing to lower treatment costs.

In December 2017, preliminary results from two Phase 1 studies in the United Kingdom and France of UCART19, an investigational allogeneic anti-CD19 CAR T-cell product, in adult and pediatric patients with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia show high complete remission rates.

The Road Ahead

CAR T-cell therapy will change the way cancer and autoimmune diseases are treated. In the second half of 2017, the first two products in this new class of therapy were approved. Autologous T cells that have been reengineered can resist the immunosuppressive effects of tumors. More than 200 clinical trials with CAR T-cell therapeutics are underway—some in combination with already-approved checkpoint inhibitors. The autologous therapies are patient-specific, personalized treatments. Frost & Sullivan believes that although new approaches to adaptive T-cell therapies remain a hurdle, the ultimate goal of increasing overall patient survival is within reach. 

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