A groundbreaking advancement in the treatment of difficult-to-treat lymphomas has emerged from the research laboratories at The University of Texas MD Anderson Cancer Center. In a first-in-human clinical study, an innovative cell therapy named RB-1355 demonstrated remarkable potential in addressing relapsed or refractory non-Hodgkin lymphomas (NHL), even in patients who had exhausted conventional treatments including CAR T cell therapy. This represents a novel paradigm shift in immunotherapy, highlighting the ability to harness and reprogram innate immune cells to mount a comprehensive anti-cancer response within the tumor microenvironment.
RB-1355 is distinguished by its unique mechanism of action which centers on the use of a patient’s own macrophages, a type of immune cell often residing in the tumor milieu. These macrophages are extracted and then subjected to an ex vivo hyperactivation process using proprietary methodologies designed to induce a robust pro-inflammatory and immune-supportive phenotype. This reprogramming effectively converts macrophages from potentially tumor-promoting actors to powerful anti-tumor effectors. Upon reintroduction into the patient’s lesions via direct intratumoral injections, these engineered macrophages reshape the tumor microenvironment by igniting a cascade of immune responses that encompass activation of neoantigen-specific T cells and B cells, thereby orchestrating a comprehensive immune assault on lymphoma cells.
One of the most compelling advantages of RB-1355 therapy is the rapid manufacturing pipeline, which allows for treatment readiness in approximately one week. This expedited timeline stands in stark contrast to other cell therapies which often require extended preparation periods, thereby making RB-1355 a more accessible option that can be deployed in a timely manner. Additionally, the therapy circumvents the need for lymphodepleting chemotherapy, a common preconditioning regimen that can cause considerable toxicity. This attribute not only enhances safety but also broadens the eligibility of patients who can receive the therapy irrespective of tumor mutational status, positioning RB-1355 as a versatile therapeutic across a spectrum of B-cell and T-cell lymphomas.
The initial clinical findings have been presented at the prestigious 2026 Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and Center for International Blood and Marrow Transplant Research (CIBMTR), showcasing promising efficacy signals. Among thirteen heavily pretreated patients enrolled in the trial, two individuals with diffuse large B-cell lymphoma (DLBCL) achieved complete remission, notably including those who had previously failed CAR T cell therapy—a population with extremely limited treatment options. These responses, including durability beyond 100 days for one patient, underscore the potential of RB-1355 to address aggressive, refractory disease in a clinical setting.
In addition to complete remissions, partial responses were also observed in patients suffering from peripheral T-cell lymphoma and mycosis fungoides, malignancies traditionally resistant to standard therapies. This breadth of activity exemplifies RB-1355’s capacity to generate meaningful clinical benefit across heterogeneous lymphoma subtypes. Equally important is the favorable safety profile reported from the trial; no dose-limiting toxicities were encountered, and only three instances of low-grade adverse effects were noted, indicating that RB-1355 is not only efficacious but also well tolerated in a fragile patient population with limited alternatives.
From an immunological standpoint, the macrophage-centric approach of RB-1355 leverages the plasticity of these myeloid cells to break the immune tolerance often established in the tumor microenvironment. By instigating an inflammatory cascade, it promotes antigen presentation and stimulates both innate and adaptive immune components. This dual activation is critical for achieving sustained anti-lymphoma activity, given the complex immune evasion strategies employed by malignant lymphocytes. Furthermore, this method does not depend on the presence of specific actionable mutations in the lymphoma cells, enabling a broad-spectrum therapeutic effect that could redefine treatment algorithms for refractory lymphomas.
The potential implications for patients are profound. Historically, relapsed and refractory non-Hodgkin lymphoma cases have represented a therapeutic dead-end with limited durable options. RB-1355’s promising early results suggest it could fill this unmet need by offering a new avenue for disease control, especially for those who have exhausted conventional chemotherapy, targeted agents, and even advanced therapies like CAR T cells. The rapid preparation and administration of RB-1355 could also minimize delays in treatment initiation, a critical factor in managing aggressive lymphomas.
Current ongoing investigations aim to optimize RB-1355 through dose escalation and repeated treatment cycles to enhance the durability of responses and potentially increase remission rates. Researchers are also exploring synergistic combinations with other immunomodulatory agents to further amplify anti-lymphoma immunity. As the body of evidence grows, RB-1355 may represent the next frontier in cell therapy by expanding the types of immune cells engineered and by circumventing the limitations associated with existing therapies that primarily target T cells.
Moreover, the development of RB-1355 reflects a growing appreciation in oncology of the tumor microenvironment’s role in cancer progression and response to therapy. Unlike approaches that solely target malignant cells, therapies like RB-1355 aim to re-educate the immune ecosystem surrounding the tumor, creating an inhospitable environment for cancer cell survival. Such strategies could herald a new class of treatments for hematologic malignancies and potentially solid tumors, enabling a more holistic immune-based eradication of cancer.
The involvement of BobcatBio in supporting this research illustrates the critical importance of collaboration between academic institutions and biotechnology enterprises in translating cutting-edge science into clinical realities. The rapid translation from bench to bedside exemplifies how innovations in cellular manufacturing and immune engineering can swiftly impact patient care in fields where therapeutic needs remain urgent.
In conclusion, RB-1355 represents an innovative and promising cell therapy that reshapes the landscape of non-Hodgkin lymphoma treatment by utilizing hyperactivated macrophages to generate a multi-dimensional immune response without the need for conventional preconditioning regimens. Early clinical data show encouraging safety and efficacy profiles in patients with relapsed or refractory disease, including those unresponsive to CAR T therapies. Continued clinical development will delineate its role within the expanding arsenal against aggressive lymphomas, potentially offering hope to a patient population with critical unmet needs.
Subject of Research: Novel cell therapy RB-1355 for relapsed and refractory non-Hodgkin lymphoma
Article Title: RB-1355: A Macrophage-Based Cell Therapy Revolutionizing Treatment of Refractory Non-Hodgkin Lymphomas
News Publication Date: 2026 (Date of presentation at ASTCT/CIBMTR 2026 Tandem Meetings)
Web References:
MD Anderson Non-Hodgkin Lymphoma Overview: https://www.mdanderson.org/cancer-types/non-hodgkin-lymphoma.html
CAR T Cell Therapy at MD Anderson: https://www.mdanderson.org/treatment-options/car-t-cell-therapy.html
Paolo Strati, M.D. Profile: https://faculty.mdanderson.org/profiles/paolo_strati.html
ASTCT/CIBMTR Tandem Meetings 2026 Program: https://www.tandemmeetings.com/
Full Abstract: https://tandem.virtual-meeting.org/programme/presentation/677607
Keywords:
Cell therapies, macrophage immunotherapy, non-Hodgkin lymphoma, relapsed lymphoma, refractory lymphoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma, mycosis fungoides, tumor microenvironment, immunotherapy, RB-1355, novel cancer treatments
Tags: advanced lymphoma treatmentCAR T cell therapy alternativescomprehensive anti-cancer responseengineered macrophages in cancerfirst-in-human clinical trialinnate immune cell activationinnovative cancer treatment methodsnon-Hodgkin lymphoma immunotherapynovel immune cell therapypro-inflammatory immune responseRB-1355 macrophage therapytumor microenvironment reprogramming
