Local delivery of antineoplastic particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer
Inventors
diZerega, Gere S. • BALTEZOR, Michael • Campbell, Sam • DECEDUE, Charles J. • MCCLOREY, Matthew • MAULHARDT, Holly
Assignees
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Publication Number
US-12329858-B2
Publication Date
2025-06-17
Expiration Date
Abstract
Disclosed are combination therapy methods useful for the therapeutic treatment of cancer by combining local administration of compositions containing antineoplastic particles, such as taxane particles, with systemic administration of compositions containing immunotherapeutic agents. Local administration methods include topical application, pulmonary administration, intratumoral injection, intraperitoneal injection, and intracystic injection.
Core Innovation
The invention is directed to a method of treating cancer in a subject by administering a first composition comprising taxane particles and a second composition comprising an immunotherapeutic agent, where the two compositions can be administered in any order or at the same time. The first composition is administered locally to an affected area selected from topical administration to a skin tumor, pulmonary administration, intratumoral administration, and intraperitoneal organ injection, and the second composition is administered systemically to the subject.
The taxane particles in the first composition have a mean particle size (number) of from 0.1 microns to 5 microns, comprise at least 95% of the taxane, and have a specific surface area (SSA) of at least 18 m2/g. The method links locally administered taxane particle properties with systemic immunotherapeutic treatment to treat cancer.
The invention also provides a kit comprising a first composition with the specified taxane particle properties and a second composition containing an immunotherapeutic agent, with instructions for administering the first composition locally and the second composition systemically. The kit supports combined local taxane particle administration together with systemic immunotherapeutic agent administration for treating cancer.
Claims Coverage
The independent claims cover two main inventive subject matter areas: a cancer treatment method combining a locally administered taxane particle composition with systemic immunotherapy, and a kit providing the local taxane particles plus the systemic immunotherapeutic composition with instructions. Across these independent claims, the inventive features include defined taxane particle properties and local administration routes, systemic immunotherapeutic administration, flexibility in timing, and instruction-based kit use.
Local taxane particles with defined particle properties and systemic immunotherapeutic treatment
A method of treating cancer in a subject by administering a first composition comprising taxane particles locally and systemically administering a second composition comprising an immunotherapeutic agent, wherein the taxane particles have a mean particle size (number) of from 0.1 microns to 5 microns, comprise at least 95% of the taxane, have a specific surface area (SSA) of at least 18 m2/g, and the steps can be conducted in any order or at the same time.
Specified local administration routes for the taxane particle composition
Administering the first composition comprising taxane particles to a subject, wherein the administration is selected from topical administration to an affected area of a skin tumor, pulmonary administration, intratumoral administration, and intraperitoneal organ injection.
Kit with local taxane particle composition and systemic immunotherapeutic agent
A kit comprising a first composition comprising taxane particles, a second composition comprising an immunotherapeutic agent, and instructions for administering the first composition locally to a subject and administering the second composition systemically to the subject.
The independent method claim centers on defined taxane particle properties used as a local administration component together with systemically administered immunotherapy, with steps allowed in any order or at the same time. The independent kit claim provides the corresponding local taxane particle composition plus a systemic immunotherapeutic agent with instructions for local and systemic administration.
Stated Advantages
Local particulate taxanes persist longer at tumor sites.
Local particulate taxanes act as local adjuvants to stimulate dendritic cells and promote systemic T-cell responses.
Potentially avoids bone-marrow suppression from intravenous taxane.
Combination efficacy criteria include greater tumor size reduction, tumor growth reduction, and/or tumor elimination compared to monotherapy.
Enhanced anti-tumor treatment outcomes are described in the provided examples, including tumor regression and greater efficacy than IV docetaxel in the stated contexts, with extensive immune-cell infiltrate and necrosis observations.
The examples state robust immune and macrophage infiltration and reduced residual viable tumor in the described xenograft contexts.
Documented Applications
Treating cancer in a subject using a first taxane particle composition locally and a second immunotherapeutic agent composition systemically.
Topical administration to an affected area of a skin tumor.
Pulmonary administration.
Intratumoral administration.
Intraperitoneal organ injection.
Kit use for administering a local taxane particle composition and systemically administering an immunotherapeutic agent.
In vivo treatment of tumors using inhaled NanoPac® to improve lung/brain tumor burden in a T-cell–deficient model with mononuclear infiltration, as described in the partial content.
In vivo intratumoral treatment using NanoDoce® (nanoparticle docetaxel) with described dose-cycle dependent regression of UM-UC-3 bladder xenografts, extensive immune-cell infiltrate, necrosis, and greater efficacy than intravenous docetaxel in the partial content.
In vivo intratumoral treatment of SRG/Rag2−/− Il2rg null renal adenocarcinoma xenografts using NanoPac® and/or NanoDoce®, with histology/IHC indicating robust immune and macrophage infiltration and reduced residual viable tumor in the partial content.
A Phase II human NSCLC study using inhaled NanoPac® staggered dosing prior to pembrolizumab, with the study described in terms of RECIST v1.1 endpoints (ORR/PFS/OS) in the partial content.
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