JP-2026514385-A - PALA local therapy for cancer

Abstract

Provided herein are compositions, systems, kits, and methods for topically applying a composition to a body area of a subject having and/or causing precancerous and/or cancerous cells (e.g., skin cancer cells), wherein the composition comprises N-phosphonacetyl-L-aspartic acid (PALA) (also known as sparphosic acid) and water, and optionally further comprising at least one nonionic surfactant.

Inventors

• マクドナルド，クリスティーン
• スターク，ジョージ

Assignees

• ザ クリーブランド クリニック ファウンデーション

Dates

Publication Date

20260511

Application Date

20240327

Priority Date

20230327

Claims (20)

1. A method for treating target precancerous cells and/or cancerous cells, The method includes topically applying the composition to a body area of a subject having and/or causing precancerous cells and/or cancerous cells, and/or adjacent to precancerous or cancerous cells, or providing the subject with the composition so that the subject can apply the composition to the body area. The method wherein the composition comprises N-phosphonacetyl-L-aspartic acid (PALA) and water, and optionally further comprises at least one nonionic surfactant.
2. The method according to claim 1, wherein the PALA is present in the composition at a concentration of about 0.1% to about 5.0% or about 1.0% to 8.0%.
3. The method according to claim 1, wherein the area of the target includes skin.
4. The method according to claim 1, wherein the precancerous cells include actinic keratosis cells.
5. The method according to claim 3, wherein the cancerous cells include melanoma or non-melanoma skin cancer cells.
6. The method according to claim 4, wherein the non-melanoma skin cancer cells are basal cell carcinoma cells or squamous cell carcinoma cells.
7. The method according to claim 1, wherein the subject is female, and the region of the subject includes the surface of the subject's vagina, and the precancerous cells and/or cancerous cells include precancerous cells and/or cancerous cells of the vagina.
8. The method according to claim 1, wherein the region of the target includes the surface of the oral cavity of the target, and the precancerous cells and/or cancerous cells include precancerous cells and/or cancerous cells of the oral cavity.
9. The method according to claim 1, wherein the subject is female, and the region of the subject includes the cervix, and the precancerous cells and/or cancerous cells include precancerous cells and/or cancerous cells of the cervix.
10. The method according to claim 1, wherein the composition further comprises a nonionic linear copolymer, optionally comprising poloxamer 188.
11. The method according to claim 1, wherein the application of the composition or the provision of the composition is repeated daily for at least 7 days, or at least 14 days, or at least 21 days.
12. The method according to claim 9, wherein the nonionic linear copolymer is present in the composition at an amount of about 50% to 90%, about 60% to 80%, about 65% to 75%, or about 70%.
13. The method according to any one of claims 1 to 12, wherein the composition further comprises a nonionic surfactant, optionally present in the composition at an amount of 10% to 30% or about 22%.
14. The method according to claim 13, wherein the nonionic surfactant comprises caprylocaproyl polyoxyl-8 glyceride, or the nonionic surfactant excipient comprises PEG-8 monoester or diester with small amounts of monoglycerides, diglycerides, and triglycerides of caprylic acid (C8) and capric acid (C10), or the nonionic surfactant comprises LABRASOL ALF.
15. The method according to any one of claims 1 to 14, wherein the composition further comprises a hydrogel agent, and the composition is in the form of a hydrogel.
16. The method according to any one of claims 1 to 15, wherein the composition further comprises isopropyl myristate, optionally present in the composition at a concentration of about 0.5% to 7%, about 1% to 5%, or about 3%.
17. The method according to any one of claims 1 to 16, wherein the composition further comprises a solubilizer and/or an emulsifier.
18. The method according to any one of claims 1 to 17, wherein the composition further comprises macrogol glycerol ricinoleate, optionally wherein the macrogol glycerol ricinoleate is KOLLIPHOR EL, and optionally the macrogol glycerol ricinoleate is present in the composition at a concentration of about 2% to 10%, about 3% to 7%, or about 5%.
19. Furthermore, the method according to any one of claims 1 to 18, comprising administering an immune checkpoint inhibitor to the subject.
20. The method according to any one of claims 1 to 19, wherein the subject is a human, a dog, or a cat.

Description

Detailed description of the invention This application claims priority to U.S. Provisional Application No. 63/492,381, filed on 27 March 2023, which is incorporated herein by reference in its entirety. This invention was implemented with government support under document W81XWH-16-1-0439 issued by the Department of Defense. The government has certain rights to this invention. [Technical Field] Provided herein are compositions, systems, kits, and methods for topically applying a composition to a subject area of body adjacent to precancerous and/or cancerous cells (e.g., skin cancer cells) that are having and/or causing such cells, wherein the composition comprises N-phosphonacetyl-L-aspartic acid (PALA) (also known as sparphosic acid) and water, and optionally further comprising at least one nonionic surfactant. [Background technology] Surprisingly, one in five Americans will develop skin cancer in their lifetime.1 Most skin cancers are caused by sun exposure and resulting from damage from ultraviolet (UV) light.2 Skin cancers are classified as either melanoma or non-melanoma (NMSC) .3 NMSC is the most common type of cancer overall and occurs in the basal cells, squamous cells, and Merkel cells of the skin.3 Basal cell carcinoma is the most common, with approximately 5.4 million people diagnosed with it annually in the United States.4 SCC is the second most common and is the most metastatic.3 SCC claims more than twice as many lives as melanoma, with an estimated 15,000 deaths annually.5 The majority of SCCs arise from actinic keratosis (AK), a precancerous lesion that affects more than 58 million Americans, and AK is one of the most common skin conditions treated by dermatologists.6 The direct treatment costs for NMSCs in the United States are estimated at $4.8 billion annually, and this does not include additional indirect costs such as wage losses.7,8 Currently, there are several FDA-approved treatments for NMSCs, each with its own advantages and limitations. The gold standard treatment is surgical removal (e.g., the Morse procedure). For precancerous cells (AKs), the gold standard is cryotherapy. These treatments can be effective for over 90% of individual lesions. However, a significant problem not addressed by localized destructive therapy (surgery or cryotherapy) is that most AK lesions occur within large areas of skin damaged by chronic sun exposure and are therefore filled with precancerous cells; this phenomenon is called "widespread carcinogenesis." To address the statistically high risk of cancer occurring in these areas, several non-invasive topical therapies are currently approved, including fluorouracil (5-FU, an antimetabolite), imiquimod (IMQ, an immunomodulator), and tilvanibrin (a microtubule inhibitor). All three topical therapies are FDA-approved for AK, with response rates of 40–80% for AK, and 5 -FU is the most effective.9 5-FU and IMQ are also FDA-approved for treating superficial BCC and are often used off-label for the treatment of superficial SCC. Each of these topical agents can treat multiple diffuse lesions (thereby addressing the "widespread carcinogenesis" problem) and often results in faster overall long-term clearance than cryotherapy, but each is also associated with strong topical skin reactions characterized by pain, burning, and skin erosion, and in some cases, hyperpigmentation or hypopigmentation of the skin. Therefore, there is still a need for improved topical NMSC therapy that is highly effective and has fewer side effects than currently available options. [Summary of the Invention] Provided herein are compositions, systems, kits, and methods for topically applying a composition to a body area of a subject having and/or causing precancerous and/or cancerous cells (e.g., skin cancer cells) and/or adjacent to such precancerous and/or cancerous cells, wherein the composition comprises N-phosphonacetyl-L-aspartic acid (PALA) (also known as sparphosic acid) and water, and optionally further comprising at least one nonionic surfactant. In certain embodiments, PALA is present in the composition at a concentration of about 0.1% to about 5.0% or 1.0% to 8.0%. In some embodiments, provided herein are methods for treating precancerous and/or cancerous cells of a subject, comprising topically applying the composition to a body area of the subject having and/or causing precancerous and/or cancerous cells (e.g., skin cancer cells) and/or adjacent to such precancerous and/or cancerous cells, or providing the subject with a composition that allows the composition to be applied to a body area, wherein the composition comprises N-phosphonacetyl-L-aspartic acid (PALA) (also known as sparphosic acid) and water, and optionally further comprising at least one nonionic surfactant. In certain embodiments, the area of study includes skin (e.g., face, arms, legs, torso, etc.). In other embodiments, cancerous cells include melanoma and non-melanoma skin cancer cells. In further embodiments, n