METHODS OF TREATING CANCER WITH A COMBINATION OF ADOPTIVE CELL THERAPY AND A TARGETED IMMUNOCYTOKINE

Smart overview of the Invention

Methods of treating cancer by combining adoptive cell therapy (ACT) with targeted immunocytokines are described. The approach involves administering a therapeutically effective amount of ACT, such as modified T cell receptors (TCR) or chimeric antigen receptors (CAR) targeting tumor-associated antigens (TAA), along with a targeted immunocytokine, like a fusion protein of IL2 and an antigen-binding domain targeting PD1. This combination enhances anti-tumor efficacy, prolongs tumor control, and improves overall survival compared to ACT alone or with non-targeted immunocytokines.

Background

Adoptive cell therapy leverages genetically modified immune cells to target cancer. It employs engineered T cells with specific receptors, such as CARs or TCRs, to recognize and attack TAAs on cancer cells. Despite its promise, ACT's success is limited due to the variability in patient response. Immunocytokines, combining antibodies with cytokines like IL2, can localize to tumor sites, enhancing immune responses. However, IL2’s broad effects and associated toxicities have restricted its use.

Combination Therapy

The disclosed methods aim to boost the effectiveness of ACT by pairing it with targeted immunocytokines. The therapy involves selecting cancer patients and administering both ACT and targeted immunocytokines. This combination results in heightened anti-tumor activity and prolonged response duration compared to ACT alone. The ACT can include various immune cells like T cells or NK cells, modified to target specific TAAs.

Targeted Immunocytokine Details

The targeted immunocytokine used in the therapy is a fusion protein comprising an immunoglobulin domain that binds checkpoint inhibitors (e.g., PD1) and an IL2 moiety. This fusion enhances the immune response by targeting specific pathways involved in tumor growth. The antigen-binding domain includes sequences from specific heavy and light chain variable regions, while the IL2 moiety can include wild type or specific fragments linked to IL2 receptor components.

Potential Embodiments

The invention encompasses various embodiments of the combination therapy. For instance, the targeted immunocytokine may include different configurations of heavy and light chain sequences or different linkers connecting IL2 moieties. These customizations allow for tailored treatments that maximize efficacy while minimizing potential side effects. Such approaches could significantly improve therapeutic outcomes for cancer patients.