For decades, people living with blood cancer were primarily treated with chemotherapy and radiation. Although they were important advances in the fight against cancer, the side effects associated with these treatments could lead to discontinuation. With a goal of achieving improved outcomes for people with aggressive and recurrent cancers, Genentech, a pioneer in oncology, developed and introduced a new class of medicines in the late 1990s called targeted antibody-based therapies. They transformed treatment paradigms and outcomes for people with non-Hodgkin’s lymphoma (NHL), the most common blood cancer. Since 1997, the survival rate for NHL has been improving due in large part to these treatment advances, and the overall 5-year survival rate in the U.S. is now 74.3%.1
Despite all that science has accomplished following that capstone development, there continues to be a need to advance the treatment of blood cancers to provide options for patients. For example, some current therapeutic regimens still require combination with chemotherapy, and others must be taken continuously until disease progression or unacceptable toxicity occurs. While there are many more very effective therapies, some remain out-of-reach to the patients who need them, as site of care requirements and/or complex and time-intensive manufacturing can make it difficult for people with blood cancer to access treatments.
As scientists’ understanding of the immune system has evolved and improved over the last 20 years, so has their ability to create even more advanced antibody-based medicines. Genentech scientists, building on the company’s expertise and capabilities in hematology, have been instrumental in researching how T-cell engaging bispecific antibodies, a type of cancer immunotherapy, might address the challenges facing people with various types of blood cancer.
“In developing new blood cancer medicines, we put patients at the center of everything we do,” said Ginna Laport*, Vice President, Global Head of Lymphoma/CLL Development. “We’re committed to raising standards of care for blood cancer by advancing the development of medicines that will improve outcomes for patients at all stages of their disease and hopefully result in long-lasting remission. Using our decades of scientific expertise, we have developed, and continue to study, several innovative blood cancer medicines that are intended to reduce the burdens associated with long-term cancer care and transform blood cancer treatment.”
In developing bispecific antibodies, in particular, Genentech scientists focused on three key areas to address the unmet needs of patients: designing new ways to target blood cancer cells, reducing the time required to start therapy, and offering fixed-duration treatments and/or chemotherapy-free regimens.
Treating Blood Cancer in a New Way: Genentech is continuing to investigate bispecific antibodies for multiple clinical applications including harnessing the patient’s own immune system to fight blood cancer. An antibody is a Y-shaped molecule that has two arms, both of which bind to the same target – for example, on a virus or bacteria. Bispecific antibodies work differently because the two arms typically bind to two different targets. For example, a bispecific antibody can be engineered to attach to a protein on the surface of T cells and B cells, both of which are immune cells. One arm of the antibody binds to the T cell protein and the other arm binds to the B cell protein. This brings the T cell near the B cell, triggering the T cell to release proteins that kill B cells, including those that cause cancer.
Ensuring Patients Receive Infusion-Ready Blood Cancer Treatment: Bispecific antibodies designed to harness the patient’s own T cells to fight blood cancer can eliminate the time needed for the complex processing that is required for CAR T-cell therapy to collect cells and genetically engineer them. This may allow patients to start treatment right away. Additionally, depending on the bispecific antibody, the individual and the type of blood cancer, the antibody may be able to be administered in an outpatient setting, which may improve access for those who are not near an academic center.
Offering Treatment Options that Can Be Given for a Fixed Course of Time: In people who have NHL, the disease often relapses or is refractory, meaning it fails to respond to treatment. Those individuals need new treatment options that can help them achieve a long-lasting complete remission (disappearance of all signs of cancer). Genentech is working to address these challenging-to-treat blood cancers with its bispecific antibodies, which are designed to be given for a fixed duration rather than until disease progression. That means people with NHL receive treatment for a finite amount of time rather than indefinitely until their cancer grows or spreads.
“We designed bispecific antibodies, a new class of immunotherapy-based medicines, to offer patients a safe and effective option with the hope of a complete remission that is accessible across different sites of care quickly,”explained Paul Carter, Genentech Fellow, Antibody Engineering Department, at Genentech.
Genentech’s bispecific antibodies offer many possibilities to improve the way serious diseases can be treated – in blood cancer and beyond.
*While Ginna Laport was an employee at the time this article was published, she has since left Genentech.