Combination taxoid nanoemulsion with immunotherapy in cancer
Inventors
Egan, James E. • Amiji, Mansoor M. • Ojima, Iwao
Assignees
Targagenix Inc • Northeastern University Boston • Research Foundation of the State University of New York
Publication Number
US-12186428-B2
Publication Date
2025-01-07
Expiration Date
2038-12-19
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A composition of an omega-3 polyunsaturated fatty acid (PUFA)-taxoid conjugate formulated in an oil-in-water nanoemulsion (NE) drug delivery system in combination with an immune-oncology (IO) agent to enhance therapeutic efficacy in refractory cancers, such as PDAC. A method of treating cancer, by administering an effective amount of a pharmaceutical composition including an omega03 PUFA-taxoid conjugate in combination with an IO agent encapsulated in an NE drug delivery system to a subject in need of treatment, and treating cancer.
Core Innovation
The present invention provides a composition comprising an omega-3 polyunsaturated fatty acid (PUFA)-taxoid conjugate formulated in an oil-in-water nanoemulsion (NE) drug delivery system, used in combination with an immuno-oncology (IO) agent, to enhance therapeutic efficacy in refractory cancers, such as pancreatic ductal adenocarcinoma (PDAC). The preferred embodiment is NE-DHA-SBT-1214, in which the taxoid conjugate DHA-SBT-1214 is encapsulated within the NE and administered in combination with an IO agent, preferably anti-PD-L1 antibody.
The invention addresses the problem that current therapies for aggressive and drug-resistant cancers—particularly PDAC—are inadequate due to tumor resistance, dense stroma, poor drug delivery, and an immunosuppressive microenvironment that limits the effectiveness of both chemotherapy and immune checkpoint inhibitors. Existing regimens offer limited improvements in survival, and immune checkpoint therapies alone have shown minimal effect due to poor T-cell infiltration and high immune suppression within the tumor mass.
By combining a PUFA-taxoid conjugate nanoemulsion, such as NE-DHA-SBT-1214, with IO agents, the invention achieves targeted delivery, efficient tumor penetration, and enhanced anti-tumor immune responses. The nanoemulsion formulation shields the conjugate from hydrolysis, enables efficient cell uptake via receptor-mediated endocytosis, and provides high drug loading and stability. The treatment both directly kills cancer cells and cancer stem cells, remodels the tumor microenvironment by increasing PD-L1 expression and T-cell infiltration, and ultimately potentiates the therapeutic effects of immunotherapies in highly refractory tumors.
Claims Coverage
The patent includes two independent claims detailing the inventive features of a pharmaceutical composition and a method of treating cancer, particularly pancreatic cancer.
Pharmaceutical composition of NE-DHA-SBT-1214 in combination with anti-PD-L1 antibody
A pharmaceutical composition comprising: - An omega-3 polyunsaturated fatty acid (PUFA)-taxoid conjugate, specifically NE-DHA-SBT-1214, - Formulated within an oil-in-water nanoemulsion (NE) drug delivery system, - In combination with an immune-oncology (IO) agent, specifically an anti-PD-L1 antibody. This composition uses the PUFA-taxoid conjugate encapsulated in a nanoemulsion to target drug-resistant cancer cells.
Method of treating cancer with NE-DHA-SBT-1214 and IO agent in nanoemulsion
A method comprising: 1. Administering an effective amount of a pharmaceutical composition containing NE-DHA-SBT-1214 as a PUFA-taxoid conjugate encapsulated in an NE drug delivery system, in combination with an IO agent, 2. Treating pancreatic cancer in a subject needing such treatment. The method may further involve increasing PD-L1 expression in the tumor microenvironment, increasing CD4+ and CD8+ tumor-infiltrating lymphocytes, down-regulating survival genes, activating p53 and p21, and treating highly drug-resistant cancers.
These inventive features define a composition and treatment method for refractory cancers, combining NE-DHA-SBT-1214 nanoemulsion and an IO agent, particularly anti-PD-L1 antibody, to achieve enhanced therapeutic efficacy, including targeting drug-resistant and stem cell populations, and improving immune response in the tumor microenvironment.
Stated Advantages
The nanoemulsion formulation allows for high drug loading efficiency, physical stability, and is suitable for both systemic and oral delivery.
Encapsulation within the nanoemulsion protects the PUFA-taxoid conjugate from hydrolysis and enables prolonged circulation and tumor targeting by passive accumulation.
NE-DHA-SBT-1214 bypasses P-glycoprotein-mediated efflux, overcoming multidrug resistance in tumor cells.
Combination therapy with NE-DHA-SBT-1214 and IO agents results in synergistic anti-tumor effects, including increased infiltration of CD4+ and CD8+ T cells and tumor regression.
The formulation uses generally regarded as safe (GRAS) materials and is amenable to large-scale GMP manufacturing.
Significant tumor suppression is achieved, with low toxicity demonstrated by no significant weight change in treated animals.
Nanoemulsion uptake by cells is efficient due to receptor-mediated endocytosis, resulting in increased potency compared to solution formulations.
Documented Applications
Treatment of refractory and highly drug-resistant cancers, such as pancreatic ductal adenocarcinoma (PDAC).
Treatment of breast, ovary, lung, head and neck, colon, rectal, melanoma, brain, prostate, leukemia, sarcomas, thyroid, Non-Hodgkin Lymphoma, bladder, gliomas, endometrial, and renal cancer.
Suppression of tumor growth and induction of tumor regression in mouse models of pancreatic cancer using combination therapy.
Targeting and killing of cancer stem cells in colon, prostate, and pancreatic tumor models.
Interested in licensing this patent?