Cell therapies

Meet the new medicines, page 5

One goal of cell therapies is to modify or replace patients’ cells.

In CAR-T cell therapy, immune cells are removed from a patient, genetically modified, then put back into the patient to fight against cancer. This approach has met with substantial success against blood cancers. For example, one CAR-T cell therapy, approved in August 2017, is now being used to treat children with acute lymphoblastic leukemia.

In cell transplants, patients are given functional cells as a replacement. When patients with blood cancers undergo chemotherapy, their blood stem cells get destroyed. Afterward, they receive a transplant of blood stem cells —collected either from themselves before chemotherapy or from a separate donor — so that they can continue to make blood.

Examples of cell replacement therapies that are in the early stages of clinical study include:

• several types of cells for corneal and retinal repair,
• certain types of neurons to replace those lost in Parkinson’s disease,
• skin cells for wound and burn repair, and
• beta cells to treat diabetes.

A different type of cell therapy takes advantage of certain cell properties to deliver drugs. For example, cancer cells have a self-homing ability, moving around the body to find tumors and spread. An HSCI scientist has co-opted this ability, using cancer cells to deliver tumor-killing proteins.

Another example is mesenchymal stem cells, which are attracted by inflammation and can home to a site of injury. They can be used to deliver small-molecule or biologic drugs.

Manufacturing cell therapies

Many cell therapies that have reached the stage of clinical trials are bespoke to each patient. Because the cells come from patients themselves, this is referred to as “autologous.”

Because of this, manufacturing is never done in bulk quantities – just one batch per patient. This process needs to be highly controlled and accurate, and the success rate extraordinarily high for a very small number of patients.  However, it is currently a very expensive process, in part because each product made is the full run.

Other types of cell therapies make use of cells from another person, and are called “allogeneic.” The manufacturing and regulatory advantage is having a product that can cover many people. But the medical risk is that the cells will be identified as foreign and rejected by the immune system in the absence of a way to  protect the them from the immune  attack.

HSCI scientists are working on a couple of ways to create cell therapies that would not be rejected by the immune system:

• One strategy is to genetically engineer a type of cell that would not be rejected by the immune system. This major achievement would make it possible to produce a treatment that is available “off-the-shelf,” offering economies of scale.
• Another strategy is to deliver cells in conjunction with protective biomaterials. For example, Semma Therapeutics, a company launched by HSCI faculty, is developing transplants of insulin-producing beta cells to treat diabetes and are using a device that shields the cells from immune attack.

If cell therapy is ever going to be available to large numbers of people, we will need disruptive breakthroughs in academic, commercial, and industrial research and development.