Targeted cancer therapy
Inventors
Lobb, Roy • Rennert, Paul David • Schiller, John Todd
Assignees
Aleta Biotherapeutics Inc • US Department of Health and Human Services
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Publication Number
US-11207339-B2
Publication Date
2021-12-28
Expiration Date
2036-10-28
Abstract
Some embodiments of the present disclosure are directed to methods that include delivering to a subject a nucleic acid encoding an antigen, wherein the nucleic acid is delivered via a tumor-selective vehicle or via intratumoral injection, and delivering to the subject an immune cell expressing a receptor that binds to the antigen.
Core Innovation
The invention provides methods and compositions for selectively targeting immune cells to tumor cells through complementary genetic engineering of the tumor cells and immune cells. Tumor cells are engineered to express antigens not expressed by normal cells or to express self-antigens at elevated levels relative to normal cells. Immune cells are engineered to express receptors that specifically bind to these antigens, enabling highly specific immunotherapeutic targeting of tumor cells.
The method involves delivering engineered nucleic acids encoding antigens to tumor cells via tumor-selective vehicles or intratumoral injection, followed by administering immune cells expressing cognate receptors that bind these antigens. The antigens may be self-antigens, non-self antigens, or recombinant chimeras thereof, and the immune cells include leukocytes engineered to express recombinant antigen receptors, such as chimeric antigen receptors (CARs).
The problem addressed is the lack of selectivity in current adoptive cell therapies, where engineered immune cells attack both tumor and normal cells due to shared antigen expression, resulting in decreased efficacy and increased side effects. By engineering tumor cells to express specific antigens and immune cells to recognize them, the invention increases the specificity and safety of cancer immunotherapy.
Claims Coverage
The claims encompass one independent claim focused on a method involving selective delivery of engineered nucleic acids encoding antigens and administration of immune cells expressing specific receptors for targeted cancer therapy.
Tumor-targeted delivery of engineered nucleic acids encoding antigens
Delivering engineered nucleic acids encoding antigens to a tumor via tumor-selective vehicles or intratumoral injection to achieve tumor cell antigen expression.
Administration of immune cells expressing chimeric receptors binding tumor antigens
Administering immune cells expressing chimeric antigen receptors that specifically bind to the antigens expressed by tumor cells, leading to targeted tumor cell killing.
Tumor-selective vehicles composed of various viral and non-viral entities
Using tumor-selective vehicles including oncolytic viruses, chimeric viruses, modified viruses targeting tumor cells, papillomaviruses, pseudoviruses, natural or synthetic polymers, peptides, nanoparticles, liposomes, and other delivery modalities for nucleic acid encapsulation and targeted delivery.
Use of a broad range of tumor antigens
Targeting tumor antigens comprising epitopes of CD19, CD20, CD21, CD22, CD45, BCMA, HER2 (ErbB2), EGFRvIII, B7-H3, B7-H6, FAP, FRa, EpCAM, GD2, ROR1, PSMA, IL13Ralpha2, and others for immune cell recognition.
Immune cells selected from diverse leukocyte populations
Employing leukocytes such as T cells, B cells, NK cells, NKT cells, or dendritic cells genetically engineered to express recombinant or chimeric antigen receptors specific for tumor antigens.
Various routes of delivery for selective targeting
Delivering tumor-selective vehicles and nucleic acids via parenteral, enteric, topical, or direct intratumoral routes to ensure localized antigen expression and effective immune targeting.
The independent claims collectively disclose a method for treating tumors by selectively expressing antigens in tumor cells via engineered nucleic acids delivered through diverse tumor-selective vehicles, and subsequently administering immune cells expressing chimeric receptors specific for those antigens. This integrated approach enables targeted elimination of tumor cells with reduced collateral effects on normal cells.
Stated Advantages
Selective targeting of tumor cells reduces off-target effects on normal cells, increasing immunotherapy specificity.
Increasing antigen expression on tumor cells enhances recognition and killing by engineered immune cells.
Use of tumor-selective vehicles enables preferential delivery of nucleic acids to tumor cells.
Complementary genetic engineering of tumor and immune cells improves efficacy of adoptive cell transfer therapies.
Documented Applications
Targeted cancer therapy involving delivery of engineered nucleic acids encoding antigens to tumor cells followed by administration of immune cells with antigen-specific receptors for selective tumor cell killing.
Adoptive cell transfer immunotherapy using immune cells engineered to express chimeric antigen receptors targeting engineered antigens on tumor cells.
Treatment of various tumor types including, but not limited to, lung cancer, melanoma, ovarian cancer, and other solid and hematological tumors via antigen delivery and immune cell targeting.
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