Immunotherapy: Can we make better CAR-Ts and bispecific antibodies?

Published: 18th March 2024

CAR-Ts and bispecific antibodies are innovative types of immunotherapies that are at the forefront of cancer research, with both approved in some countries to treat patients with multiply relapsed follicular lymphoma (FL). To read more on immunotherapies and understand what CAR-Ts and bispecific antibodies are, read our last deep dive on “Immunotherapy: A breakthrough in follicular lymphoma treatment”.

The challenge now is: how do we improve these treatments to ensure long-lasting effectiveness, fewer side effects, and ensure they are accessible to people across the world? Current research is focusing on more aspects of the cancer cells and their surroundings in the body to address challenges like resistance. Additionally, exploring different, quicker, and more cost-effective manufacturing processes could minimise their side effects and increase accessibility for more people worldwide.

The Follicular Lymphoma Foundation (FLF) is at the forefront of FL research, investigating different aspects to improve immunotherapy. Current ongoing and future studies funded by the FLF CURE FL Awards have exciting potential to address the above-mentioned challenges and pave the way for a cure for FL.  

Where are we at now?

Of the three CAR-T therapies approved for FL in the US, data from real-world studies indicate that many patients are experiencing highly positive responses lasting several years or more. While it is still too early to reliably assess the time until disease progression (progression-free survival), it is expected to exceed four years. In bispecific antibody trials, the long-term effectiveness has not been established, but it may be comparable. However, due to patient characteristics within these trials, direct comparisons are not feasible. Some studies have utilised bispecifics as an initial treatment, either alone or in combination, showing the potential to reduce the necessity for chemotherapy or even enable a chemotherapy-free approach.


The next step in this research is to improve outcomes even further, obtaining higher response rates and, importantly, longer durations of response.

Dr Mitchell Smith, FLF Chief Medical Officer

Why do we need to improve CAR-Ts and bispecific antibodies? 

Continuous improvements in CAR-T cells and bispecific antibodies are essential to enhance their effectiveness in treating cancer and FL, providing more options for a larger global population. This imperative includes overcoming challenges such as:

·     Cancer cell resistance: Various factors contribute to resistance, including genetic mutations and the (micro)environment surrounding cancer cells, making treatments less effective, or diminishing treatment efficacy, over time.

·       Reducing side effects: Enhancing patients’ quality of life.

·       Access and affordability: Developing faster and more cost-effective manufacturing processes to increase accessibility for more individuals.

·       Promoting diversity and equity in accessing these treatments: Reducing disparities in access to cutting-edge therapies.

·       Expanding the range of cancers that can be effectively treated: Making treatments applicable to a wider variety of patients and cancer types.


Can we enhance CAR-Ts and bispecific antibodies? 

By targeting different components of cancer cells or the surrounding environment, researchers aim to improve the effectiveness of these treatments and overcome challenges like resistance. For instance, CAR-T cells currently target specific cell-surface proteins present on B-cells, such as CD19 and CD20 commonly found in FL, and researchers are exploring approaches that involve attacking multiple targets at the same time. In bispecific antibody trials, new versions targeting CD19 instead of CD20 are being tested. Both therapies are also investigating diverse targets to broaden their applicability to treating various cancer types.

Every stage in CAR-T generation and manufacturing involves processes for enhancement, all actively under investigation with numerous innovative approaches. Novel manufacturing techniques hold the potential to reduce side effects, while quicker and more cost-effective methods may expand access to these treatments for more patients.

Advancements in cellular engineering are identifying ways to boost the killing capacity of T-cells, a crucial element of CAR-T therapy. Robust screening methods help identify areas for improving T-cell function, thereby enhancing the effectiveness of CAR-T. These strategies could also be utilised to develop “off-the-shelf” CAR-T products, making them more readily available and accessible to a wider range of patients.

What is the FLF doing? 

The FLF is actively driving innovative research projects through our CURE FL Awards programme, focusing on CAR-T and bispecific molecules. These awards are currently supporting four ongoing studies and future studies that specifically target challenges in the field, holding the potential to significantly contribute to finding a cure for FL.

The CURE FL Awards programme is a unique research grant initiative aimed at catalysing scientific research to develop improved treatments and potential cures for FL. The programme brings together leading clinical scientists and researchers globally to work on innovative and impactful research projects. By collaborating with partners such as Centre for Strategic Philanthropy at the Milken Institute and the Leukemia & Lymphoma Society, the FLF is actively working to accelerate breakthroughs in FL and address the urgent need for improved therapies.

For more detailed scientific insights into the current and future FL research landscape, please explore publications by Dr Mitchell Smith, FLF Chief Medical Officer, here and specifically his related article FLF’s Chief Medical Officer’s top highlights from American Society of Hematology (ASH) 2023 Annual Meeting” where he expands on this topic.


Disclaimer: This article serves to inform patients about the potential of immunotherapy in treating follicular lymphoma. Patients are advised to consult with their healthcare providers for personalised treatment recommendations and considerations.