This story also appears on STAT.
Non-Hodgkin’s lymphoma (NHL), one of the most common blood cancers in the U.S.,1 is actually a group of diseases with more than 60 identified subtypes.2 Each subtype is characterized by distinct clinical presentations, biological profiles and underlying genetics, and requires a different approach.
Scientists at Genentech and across the scientific community are working to better understand NHL with the goal of offering patients with diverse subtypes of NHL treatment solutions that are precisely right for them. Recent discoveries have laid the foundation for two novel treatment approaches for these complex, difficult-to-treat blood cancers – antibody-drug conjugates (ADCs) and T-cell engaging bispecific antibodies, a type of cancer immunotherapy.
More options are needed
All forms of NHL are driven by malignant transformation of lymphoid cells, primarily within the lymph nodes, but also in the bone marrow, spleen and gastrointestinal tract.3 Historically, NHL has been treated with chemotherapy given by itself or in combinations, sometimes with other types of treatment such as immunotherapy or radiation.
FDA-approved treatment options for NHL are currently limited, and patients often relapse following initial treatment or experience resistance. Treatment approaches are sometimes limited depending on disease stage and patient characteristics such as age, frailty and comorbidities.4
The origins of the cancer help determine the subtype and treatment course.6 B-cell NHL arises from B cells,5 but other subtypes may arise from T cells or natural killer (NK) cells, known for their ability to directly kill cancer cells. Although chemotherapy can be effective, its toxicity can be harmful to all cells, not just cancer cells.7 Chimeric antigen receptor (CAR) T-cell therapy, which uses a patient’s reengineered immune cells to attack cancer, can be effective, but logistical challenges may limit its wide use across a variety of treatment settings, including community-based care.8
Pioneering science
The introduction of antibody immunotherapy has changed the cancer treatment landscape, and its potential is only starting to be fully tapped. ADCs and bispecific antibodies have been developed based on learnings from antibody science and offer hope to patients and physicians alike. These approaches may offer new treatment options for cancers such as diffuse large B-cell lymphoma (DLBCL), the most common type of aggressive NHL. An estimated 40% of patients with this type of NHL relapse after initial treatment.9
ADCs deliver chemotherapy directly to cancer cells, mitigating some of the toxicity and side effects associated with systemic chemotherapy.10 An early innovator in ADCs, Genentech is credited with developing a technology that helped enable ADCs to directly target disease-causing cells. Genentech scientists engineered a novel linker that can be used interchangeably with different antibody-based medicine combinations. This adaptable system allows for mixing and matching of antibodies and linkers to develop the most stable and effective ADC medicine. Genentech has already received FDA approval for two ADCs.
A newer innovation in immunotherapy, T-cell engaging bispecific antibodies are designed to recruit the immune system to destroy cancer cells by engaging with two different targets simultaneously – for example, CD20 on a blood cancer cell and CD3 on a T cell.11 Because this treatment bypasses the need for cell collection and genetic engineering, it holds the potential to be administered in community settings at local facilities rather than just at large academic treatment centers, increasing accessibility for patients. This treatment may better meet the needs of some people with blood cancer.
Although the idea for creating bispecifics had been around for nearly half a century before the first bispecifics were developed, the difficulty in actually creating them hindered progress. With a typical antibody, both “halves” of the Y shape are identical. To successfully engineer a bispecific, each “half” must be designed to engage separate molecular targets. Additionally, these pieces from two different antibodies must assemble in a particular way to be effective.
Genentech developed a technology called “knobs-into-holes” that solved the challenge of assembling bispecifics in a particular way to engage separate molecular targets, allowing for the innovation seen today.12 Genentech is now working to bring bispecific medicines to people with NHL as early as this year.
Bispecifics and ADCs are two key approaches that have the potential to help improve the treatment experience, and ultimately outcomes, for patients, including the estimated 80,000 people in the U.S. diagnosed with NHL in 2021.13 New treatments create opportunity to revolutionize the way the medical community treats blood cancers.
To learn more, visit Genentech’s Hematology Hub.