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Publication Number
US-11813279-B2
Publication Date
2023-11-14
Expiration Date
Abstract
One aspect of this disclosure is directed to a method for treating a cancer in a subject in need thereof by administering to the subject at least a first compound and a second compound together or separately. The first compound is an effective amount of a checkpoint inhibitor optionally with at least one pharmaceutically acceptable carrier. The second compound is an effective amount of an Anti-Tumor Immune Enhancer (ATIE) optionally with at least one pharmaceutically acceptable carrier. The compounds can be administered together or separately.
Core Innovation
The invention relates to a method for treating cancer by administering an anti-PD-L1 antibody together with or separately from rintatolimod. The method applies to cancers selected from pancreatic cancer, renal cell carcinoma, colorectal cancer and melanoma, in a subject in need thereof, with each compound provided in an effective amount and optionally with at least one pharmaceutically-acceptable carrier.
rintatolimod is provided as an Anti-Tumor Immune Enhancer (ATIE) based on a TLR3-activating mismatched dsRNA. The approach addresses the checkpoint inhibitor problem associated with immunologically “cold” tumors by shifting the tumor microenvironment toward increased Teff cells (CD8+ and CD4+) and decreased Treg cells.
The described rationale includes immune biomarker effects such as changes in CXCL10 and CCL22 and improved Teff/Treg marker ratios in tumor samples, along with synergy or additive effects with the checkpoint inhibitor. The document further describes that rintatolimod can be administered concurrently or sequentially with anti-PD-L1 blockade, and that the treatment can be evaluated using clinical and pharmacodynamic measures such as RECIST and immune monitoring.
Claims Coverage
The provided material includes two independent claims. Both independent claims are directed to methods of treating cancer in a subject using an effective amount of an anti-PD-L1 antibody and an effective amount of rintatolimod, with either together or separately administration, and with optional pharmaceutically-acceptable carriers.
Treating selected cancers with anti-pd-l1 and rintatolimod
A method for treating a cancer selected from pancreatic cancer, renal cell carcinoma, colorectal cancer and melanoma in a subject in need thereof, comprising administering to the subject at least a first compound and a second compound together or separately, wherein the first compound comprises an effective amount of an anti-PD-L1 antibody optionally with at least one pharmaceutically-acceptable carrier, and wherein the second compound is an effective amount of rintatolimod optionally with at least one pharmaceutically-acceptable carrier.
Contacting cancer with anti-pd-l1 and rintatolimod
A method for treating a cancer selected from pancreatic cancer, renal cell carcinoma, colorectal cancer and melanoma in a subject in need thereof, comprising contacting the cancer to a first compound and a second compound together or separately, wherein the first compound comprises an effective amount of an anti-PD-L1 antibody optionally with at least one pharmaceutically-acceptable carrier, and wherein the second compound is an effective amount of rintatolimod optionally with at least one pharmaceutically-acceptable carrier.
Across the independent claims, the core inventive coverage is the combined use of an effective amount of an anti-PD-L1 antibody and an effective amount of rintatolimod in a subject having selected cancers, with administration or contacting either together or separately and optionally with pharmaceutically-acceptable carriers.
Stated Advantages
Synergistic anticancer effect, including greater inhibition of tumor-cell proliferation than rintatolimod alone, anti-PD-L1 antibody alone, or their additive effect.
Improved survival and/or time-to-progression in mouse models with anti-PD-L1 blockade for specified cancers.
Increased RECIST responses when used with anti-PD-L1 in a B16 melanoma model.
Immune biomarker effects, including increased CXCL10:CCL22 ratio and improved Teff/Treg marker ratios in colorectal tumor samples.
Monotherapy tumor inhibition/survival effects reported in renal and bladder xenograft models.
Documented Applications
Combination cancer immunotherapy applying anti-PD-L1 antibody together with rintatolimod to treat pancreatic cancer, melanoma, colorectal cancer, and renal cell carcinoma.
Preclinical testing in mouse models including pancreatic and colorectal cancer, with reported improved survival and/or time-to-progression with anti-PD-L1 blockade plus rintatolimod.
A B16 melanoma model reporting increased RECIST responses with anti-PD-L1 and rintatolimod combination.
Tumor sample immune monitoring in colorectal tumor samples, including measurements involving CXCL10 and CCL22 and Teff/Treg marker ratios.
Renal and bladder xenograft models reporting monotherapy tumor inhibition/survival effects.
Early clinical/immune monitoring pilot cohort described in the partial content summary, using immune monitoring alongside the combination immunotherapy.
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