Over the past several decades, scientists have made many leaps forward in the quest to develop more effective medicines to treat or prevent disease – for example, small molecules that change the inner workings of cells; therapeutic antibodies that precisely target proteins on the surface of cells; and gene therapy that provides cells with instructions to make specific proteins. Each of these modalities focuses on changing the function of cells in our body. But what if we could alter and deploy cells themselves to help us fight disease more effectively? What if we could transplant cells to regenerate tissue and restore lost function? Revolutionary advancements in science are now enabling us to explore the full potential of this novel approach and turn cells into living medicines.

This area of therapeutics, known as cell therapy, aims to replace or enhance cells so they can effectively carry out vital roles and treat – or even cure – diseases. Over the past several years, cell therapy has become a powerful treatment option for certain hematologic cancers, but this area is in its infancy; much work will be required to realize its broader potential. Research and early development units at Genentech (gRED) and Roche pharma (pRED) are committed to advancing biological research, technology innovations and clinical development to accelerate the discovery and development of new cell therapies in oncology, ophthalmology, neurology, hematology, and immunology.

“Cell therapy has the potential to change how we treat disease,” says James Sabry, Global Head of Roche Pharma Partnering. “At Roche and Genentech, our interest in cell therapy is directly tied to our commitment to inventing pioneering medicines with substantial patient benefit. To complement our own efforts, we are bridging different scientific approaches and expertise through collaborations that will provide us with the toolkit necessary to tap into the full potential of cell therapy.”

By working together, we are enabling scientists to make potentially groundbreaking discoveries that may address key obstacles in cell therapy – including genetic modification, scalability and limits on what diseases can be treated. “This is a challenging field, but our engagement in advanced technologies and our understanding of human biology will move us forward as we aim to increase patient benefit,” says Andy Chan, Senior Vice President, Research Biology at Genentech. “We have the scientific fortitude to address the challenges and realize their full potential."

Read on to learn more about our therapeutic approaches and collaborations that are driving the future of cell therapy.

Neoantigens | Enhancing T Cells | Allogeneic Car-T | Off-the-Shelf | Regenerative Medicine

An antigen is a protein that can induce an immune response in the body. While tumor cells share a majority of their DNA with healthy cells, they also carry numerous unique mutations. Some of these mutations result in the production of new antigens, called “neoantigens,” which offer a seek-and-destroy signal for our immune system, killer T cells in particular, to home in on.

Genentech and Adaptive are working together to engineer T cells that target neoantigens – a potentially powerful approach that harnesses a patient’s own immune system to fight cancer. Neoantigen-directed T cell therapy requires scientists to first identify naturally-occurring T cell receptors (TCRs) that can recognize neoantigens, and then engineer those receptors back into a patient’s own T cells so they can attack cancer. Because this approach uses an individual’s own cells, it is known as an autologous cell therapy.

We are fusing our expertise in high-throughput sequencing, machine learning and cancer immunology to identify and select clinically-optimal TCRs to develop cancer cell therapies. One aspect of the collaboration focuses on screening and identification of therapeutic TCRs at unprecedented scale to target a common shared neoantigen present in many cancer patients. Another aspect focuses on a fully personalized therapeutic approach that can include several patient-specific TCRs that target each patient’s own unique tumor neoantigens. This approach involves taking a patient’s own immune cells and screening for the most relevant TCRs. Once identified, these TCRs may be engineered and manufactured into personalized cell therapies that could significantly enhance targeted tumor killing for people with cancer. If successful, this type of therapy could be applicable to all cancer patients regardless of the type of cancer they have.

“There is great potential for the next-generation of cell therapies to hopefully treat a broader set of tumor types, while making them more easily accessible to patients around the world,” says Patrick Schleck, Head of Oncology, Roche Pharma Partnering. “The pioneering scientific advances we’re making provide the opportunity to advance personalized cell therapies by tailoring and precisely targeting treatment to a patient’s own unique tumor-specific neoantigens.”

Read more about the collaboration here.

Cell therapies have been deployed successfully against certain cancers, but solid tumors have proven more difficult to target with this approach. Complex immunological defense systems within and surrounding solid tumors thwart the activity of immune cells programmed to attack the tumors.

Genentech and Arsenal Bio are collaborating to leverage their expertise in cancer immunology, genomics and computational approaches – including machine learning – to hopefully identify novel biology for engineering of T cells that has the potential to evade immune defense mechanisms of solid tumors.

The approach involves high-throughput techniques to characterize T cell functional states that are paired with machine learning to discover potential cell modifications at an unprecedented scale. The convergence of detailed biological data and sophisticated computational methods has the potential to advance the design, development and testing of next-generation cell therapies effective at treating solid tumors.

“This is the next step in T cell engineering,” says Ira Mellman, Vice President of Cancer Immunology at Genentech. “We are identifying which genetic enhancements will have the most beneficial effects so we can design the most optimal therapies. Furthermore, this collaboration will uncover important new discoveries about basic T cell biology and immunology – paving the way for future therapeutic approaches.”

Read more about the collaboration here.

Chimeric antigen receptor T cell (CAR-T) therapy is an established class of T cell therapy with proven success against certain blood cancers. But the current approach is time-consuming and requires patients to wait for their T cells to be collected and engineered in the lab before they can begin treatment. The current reliance on patient-derived cells also limits the ability to use sophisticated engineering techniques to improve performance.

Roche and Poseida are working together to develop the next generation of off-the-shelf, or allogeneic, CAR-T cell therapies to address medical needs for patients with certain blood cancers. The collaboration involves use of proprietary technologies and manufacturing processes that have the potential to deliver advanced healthy donor-derived cell therapies at a scale that can readily reach most hematology patients.

Progress is well underway on investigational therapies for the treatment of multiple myeloma, acute myeloid leukemia and B cell malignancies. In addition to developing potential T cell therapies that can address high unmet medical needs for a broad patient population with blood cancers, this collaboration also includes a research program to develop next generation allogeneic T cell therapies, designed to ensure a continued investment into innovation in the future.

“I’m really excited about working together with Poseida, a biotech with a strong expertise mainly in cell therapy, gene therapy and also gene editing. If we look at the potential impact on patients of an allogeneic CAR-T therapy, a possible treatment can potentially be administered in an outpatient setting, which is very important for the convenience of patients and may reduce treatment burden,” says Marion Ott, Global Head of Myeloid and Multiple Myeloma Hematology at Roche.

Read more about this collaboration here.

Autologous cell therapies typically require harvesting, preserving, engineering and reintroducing cells from each patient. While these cell therapies may lead to remission or even cures in some cancer patients, these challenging and complex procedures can limit access for the people who need these therapies.

Genentech and Adaptimmune are teaming up to overcome these challenges through the development of off-the-shelf, or allogeneic, cell therapies that leverage engineered T cells from our immune system.

These allogeneic approaches start with induced pluripotent stem cells (iPSCs) derived from mature cells that were coaxed to return to an immature state that allows them to become any type of cell. These iPSCs are then differentiated into T cells with an enhanced ability to combat cancer. iPSCs are derived from adult cells from a donor and then are used to create a bank that can be used to generate cell populations tailored to fight specific cancers. Having a single, reproducible source of these T cells could potentially allow physicians to treat multiple eligible patients on demand.

“The use of engineered cells is the future of medicine, and developing off-the-shelf treatments using iPSCs represents the next step in cell therapy,” says Ira Mellman, Vice President of Cancer Immunology at Genentech. “Our collaboration with Adaptimmune will allow us to engineer iPSCs in an iterative fashion, improving them as needed, and through our work with other partners, make them specific to each patient. Importantly, this approach could greatly reduce variability and cost, helping to realize our goal of making these potentially powerful therapies affordable and accessible.”

Read more about this collaboration here.

Cell therapy has the exciting potential to treat a range of illnesses, including vision-threatening eye disease.

Advanced dry age-related macular degeneration (AMD) with geographic atrophy (GA) is a serious eye disease that develops when specific retinal cells die off or degenerate, causing vision loss. While current therapeutic strategies in GA aim to slow disease progression, cell therapy has the potential to go further.

“Cell-based therapies provide the possibility to replace dying or damaged eye cells with new healthy ones,” says Tom Zioncheck, Head of Neuroscience, Ophthalmology, and Rare Diseases at Roche Pharma Partnering. “Our aim is to repair the underlying cellular structure of the retina – a thin layer of tissue that lines the back of the eye – to preserve and even restore vision.”

Genentech and Lineage Cell Therapeutics are teaming up to create allogeneic retinal pigment epithelial (RPE) cells that may be delivered under the retina to either replace or support cells that are dysfunctional or absent due to degenerative disease.

“This approach may allow for a robust supply of cells and the ability to have doses manufactured ahead of time, so they are readily available for patients,” says Seppi Lin, Vice President, Head of OMNI Early Clinical Development at Genentech. “The eye is an ideal organ to investigate cell therapy as regenerative medicine because cell delivery is relatively more straightforward than that to other organs.”

The hope is that this investigational treatment option could not only slow down progression of the dry form of AMD, but also restore function to the retina. OpRegen RPE cell therapy will support Roche and Genentech’s journey in ophthalmology through the development of a pioneering regenerative retinal cell therapy in the clinic, as well as through new research into the biology of the retina, the retinal microenvironment and the development of new biomarkers.

Read more about the collaboration here.