Anti-CD30 antibody and chimeric antigen receptor comprising thereof
Inventors
Lee, Jong-Seo • Kim, Jong-Hoon • Kim, Ki Hyun • Lee, Hyun-Jong • Ruella, Marco • GURUPRASAD, Puneeth
Assignees
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Publication Number
US-12668640-B2
Publication Date
2026-06-30
Expiration Date
Abstract
Disclosed herein are a novel antibody and an antigen binding fragment thereof that targets CD30 to treat cancer, a chimeric antigen receptor, and a use thereof. The antibody, which binds specifically to CD30 that is highly expressed in cancer cells (specifically blood cancer), is very low in sequence homology with the CDR sequences of conventional CD30 targeting antibodies and thus has a unique sequence. Cells that express the chimeric antigen receptor including the anti-CD30 antibody or the antigen binding fragment responds to CD30-expressing positive cells to induce immune cell activity, thus finding advantageous applications as a CAR-immune cell product.
Core Innovation
The invention provides an anti-CD30 antibody or an antigen binding fragment thereof comprising an immunoglobulin heavy-chain variable region domain and an immunoglobulin light-chain variable region domain. The heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3, and the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3, with amino acid sequences defined by multiple enumerated SEQ ID NO sets.
The invention also provides a CD30-specific chimeric antigen receptor comprising the anti-CD30 antibody or an antigen binding fragment thereof, a transmembrane domain, and an intracellular signaling domain. The CAR uses the defined heavy-chain variable region domain and light-chain variable region domain of the anti-CD30 antibody or antigen binding fragment thereof, with intracellular signaling domain components selected from 4-1BB, CD28, OX40, and CD3, including combinations.
The document describes identification and functional evaluation of CD30-binding antibody clones and corresponding CD30-CAR-T constructs. It describes determining CD30 binding specificity relative to other TNFR family members, and evaluating CD30-CAR-T activity including CAR expression, cytotoxicity against CD30+ cell lines, IFN- release, off-target testing on CD30 cells, and in vivo antitumor efficacy using NSG mice with HDLM-2 xenografts.
Claims Coverage
The provided claim set includes two independent claims. Across these, the main inventive coverage is the definition of anti-CD30 variable regions by enumerated HCDR/LCDR amino acid sequence sets, and the incorporation of those defined anti-CD30 binding domains into a CD30-specific chimeric antigen receptor architecture including a transmembrane domain and an intracellular signaling domain.
Anti-cd30 antibody with enumerated hcdr and lcdr sequence sets
An anti-CD30 antibody or an antigen binding fragment thereof comprising an immunoglobulin heavy-chain variable region domain and an immunoglobulin light-chain variable region domain, wherein the heavy-chain variable region domain comprises HCDR1, HCDR2, and HCDR3 with amino acid sequences of SEQ ID NO: 1, 2, and 3, and wherein the light-chain variable region domain comprises LCDR1, LCDR2, and LCDR3 with amino acid sequences of SEQ ID NO: 4, 5, and 6, with alternative enumerated HCDR and LCDR sets.
Cd30-specific chimeric antigen receptor with defined antibody variable regions plus transmembrane and intracellular signaling domains
A CD30-specific chimeric antigen receptor comprising an anti-CD30 antibody or an antigen binding fragment thereof, a transmembrane domain, and an intracellular signaling domain, wherein the anti-CD30 antibody or the antigen binding fragment comprises a heavy-chain variable region domain with HCDR1, HCDR2, and HCDR3 and a light-chain variable region domain with LCDR1, LCDR2, and LCDR3, with the HCDR and LCDR amino acid sequences selected from the enumerated SEQ ID NO sets.
The independent claim coverage centers on anti-CD30 binding specificity implemented through explicitly enumerated HCDR/LCDR amino acid sequence sets, and on using those defined binding domains as the extracellular recognition element of a CD30-specific chimeric antigen receptor that further includes a transmembrane domain and an intracellular signaling domain.
Stated Advantages
Immune activation/cytotoxicity against CD30-positive cells as stated in the provided summary content.
Use as a CAR-immune cell therapy product as stated in the provided summary content.
Documented Applications
Treatment of CD30-expressing cell-associated diseases by administering a pharmaceutical composition including the anti-CD30 antibody or antigen binding fragment thereof, and/or by use of CD30-specific CAR-expressing effector immune cells, as stated in the provided summary content and claim context.
Binding assessment and specificity evaluation of CD30-binding antibody clones, including determination of EC50 and CD30-specificity versus other TNFR family members.
Functional evaluation of CD30-CAR-T constructs, including CAR expression, cytotoxicity against CD30+ cell lines, and IFN- release, with off-target testing on CD30 cells.
In vivo antitumor efficacy evaluation in NSG mice using HDLM-2 xenografts.
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