公开(公告)号：US20240299541A1

公开(公告)日：2024-09-12

申请号：US18549503

申请日：2022-03-09

Applicant: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Mikko Siurala ,  Carl H. June ,  Avery Posey ,  Antoni Ribas ,  Anusha Kalbasi

IPC: A61K39/00 ,  A61K35/761 ,  A61K48/00 ,  A61P35/00 ,  C07K14/55 ,  C07K14/715 ,  C12N5/0783 ,  C12N15/86

CPC classification number: A61K39/4611 ,  A61K35/761 ,  A61K39/4631 ,  A61K39/4637 ,  A61K39/464419 ,  A61K39/464468 ,  A61K48/0075 ,  A61P35/00 ,  C07K14/55 ,  C07K14/7155 ,  C12N5/0636 ,  C12N15/86 ,  C07K2319/03 ,  C07K2319/75 ,  C12N2510/00 ,  C12N2710/10032 ,  C12N2710/10043

Abstract: The present disclosure provides orthogonal chimeric cytokine receptor/orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

公开(公告)号：US20230310502A1

公开(公告)日：2023-10-05

申请号：US18160825

申请日：2023-01-27

Applicant: The Regents of the University of California

Inventor： Theodore Lee Roth ,  Eric Shifrut ,  Alexander Marson ,  Cristina Puig Saus ,  Antoni Ribas

IPC: A61K35/17 ,  C07K14/725 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/90

CPC classification number: A61K35/17 ,  C07K14/7051 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/907 ,  C12N2310/20

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

公开(公告)号：US11275080B2

公开(公告)日：2022-03-15

申请号：US14933853

申请日：2015-11-05

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Paul C. Tumeh ,  Antoni Ribas

IPC: C07K16/00 ,  G01N33/50 ,  C07K16/28 ,  A61K39/00

Abstract: A method of analyzing a biological sample from a subject that has a tumor or cancer, comprising: determining, for target cells having a phenotype of interest spatial resolution of the target cells, density of the spatially resolved target cells in the sample; and proximity between spatially resolved target cells of interest in the sample; and determining an overall score based at least in part on the preceding parameters. A method for identifying a patient as a responder to single agent anti-PD-1 or anti-PD-L1 therapy is provided. Similar methods are provided for detecting adaptive immune resistance, the presence of cancer in a patient sample, determining efficacy of cancer therapy, and determining response to and monitoring the efficacy of cancer therapy.

公开(公告)号：US20210324035A1

公开(公告)日：2021-10-21

申请号：US17273192

申请日：2019-09-04

Applicant: The Regents of the University of California ,  California Institute of Technology ,  The Olivia Newton-John Cancer Research Institute

Inventor： Owen N. Witte ,  Jami McLaughlin Witte ,  Antoni Ribas ,  Lili Yang ,  Michael T. Bethune ,  Jonathan Cebon ,  Katherine Woods ,  Ashley J. Knights ,  David Baltimore

IPC: C07K14/725 ,  A61K35/17 ,  C12N15/86 ,  C12N5/0783 ,  A61P35/00

Abstract: Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we have developed an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.

公开(公告)号：US10744116B2

公开(公告)日：2020-08-18

申请号：US16084911

申请日：2017-03-16

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Roger S. Lo ,  Willy Hugo ,  Antoni Ribas ,  Jesse Zaretsky

IPC: G01N31/00 ,  A61K31/385 ,  C12Q1/6886 ,  C07K16/28 ,  G16B20/00 ,  A61P35/00 ,  G16B5/00 ,  G16B25/00 ,  A61K31/337 ,  A61K31/427 ,  A61K39/395 ,  A61K45/06 ,  C12Q1/686 ,  G16B25/10

Abstract: Methods of predicting or detecting sensitivity to therapeutic effects of anti-PD-1 therapy in a patient suffering from melanoma, as well as for selecting somatic mutanomes and transcriptomes of melanoma biopsies. A tumor sample obtained from the patient is assayed for a measure of anti-PD-1 therapy sensitivity via, for example, whole transcriptome sequencing, antibody based protein quantifications, mass spectrometry based protein quantification, targeted mRNA sequencing, real-time RT-PCR, Sanger sequencing, targeted sequencing and/or whole exome/genome sequencing. Samples are selected that exhibit a higher first enrichment similarity score and/or a lower second enrichment similarity score, and/or at least one measure of sensitivity. A patient whose sample was selected herein as a candidate for anti-PD-1 therapy is thereby identified. The method of the invention can further comprise treating the patient with anti-PD-1 therapy, optionally in conjunction with combinatorial therapy.

公开(公告)号：US10711312B2

公开(公告)日：2020-07-14

申请号：US15648423

申请日：2017-07-12

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Antoni Ribas ,  Jesse Zaretsky ,  Daniel Shin ,  Angel Garcia-Diaz ,  Blanca Homet Moreno

IPC: C12Q1/6886 ,  C07K16/28 ,  A61K39/00

Abstract: Disclosed herein are methods of treating or assessing cancer in a subject wherein it has been determined whether the cancer comprises a loss of function mutation or disruption in an immune pathway. The loss of function mutation or disruption can be in JAK1 or JAK2. The loss of function mutation or disruption can be in B2M. The methods can include administering an immune checkpoint therapy such as anti-PD1 or anti-PDL1. The methods can include administering an alternative therapy to an immune checkpoint therapy. In some aspects, the method includes determining whether the cancer comprises a loss of function mutation or disruption in an immune pathway.

公开(公告)号：US10201597B2

公开(公告)日：2019-02-12

申请号：US15516012

申请日：2015-09-29

Applicant: The Regents of the University of California

Inventor： Antoni Ribas ,  Richard C. Koya ,  Thinle Chodon

IPC: A61K39/00 ,  C07K14/725 ,  C12N15/86

Abstract: The invention relates to methods and materials that can be used to product cytotoxic T cells that target cancer cells expressing the cancer-testis antigen NY ESO-1. Illustrative embodiments of the invention include peripheral blood stem cells transduced with a lentiviral vector that comprises a codon optimized TCR alpha and beta chain polypeptides specific for NY ESO-1. These gene-modified cells are useful, for example, in a hematopoietic stem cell transplantation setting to treat patients diagnosed with NY ESO-1 positive cancers.

公开(公告)号：US20180326033A1

公开(公告)日：2018-11-15

申请号：US15516012

申请日：2015-09-29

Applicant: The Regents of the University of California

Inventor： Antoni Ribas ,  Richard C. Koya ,  Thinle Chodon

IPC: A61K39/00 ,  C07K14/725 ,  C12N15/86

CPC classification number: A61K39/001188 ,  A61K39/0011 ,  A61K2039/5156 ,  A61K2039/5158 ,  A61K2039/572 ,  A61K2039/876 ,  C07K14/7051 ,  C12N5/0638 ,  C12N15/86 ,  C12N2501/515 ,  C12N2510/00 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2800/22

Abstract: The invention relates to methods and materials that can be used to product cytotoxic T cells that target cancer cells expressing the cancer-testis antigen NY ESO-1. Illustrative embodiments of the invention include peripheral blood stem cells transduced with a lentiviral vector that comprises a codon optimized TCR alpha and beta chain polypeptides specific for NY ESO-1. These gene-modified cells are useful, for example, in a hematopoietic stem cell transplantation setting to treat patients diagnosed with NY ESO-1 positive cancers.

公开(公告)号：US12213977B2

公开(公告)日：2025-02-04

申请号：US16625075

申请日：2018-06-27

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Thomas G. Graeber ,  Jennifer Tsoi ,  Antoni Ribas ,  Lidia Robert ,  Nicolaos Palaskas

IPC: A61K31/517 ,  A61K31/437 ,  A61K35/17 ,  A61K45/06 ,  C07K16/28

Abstract: The current methods and compositions provide for a novel therapeutic method for treating patients diagnosed with melanoma, especially those that have become resistant to certain other therapies. Accordingly, certain aspects of the disclosure relate to a method for treating melanoma in a subject, the method comprising administering a composition comprising a ferroptosis-inducing agent or other dedifferentiated melanoma-targeting agent to the subject.

公开(公告)号：US11331346B2

公开(公告)日：2022-05-17

申请号：US17390673

申请日：2021-07-30

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Theodore Lee Roth ,  Eric Shifrut ,  Alexander Marson ,  Cristina Puig Saus ,  Antoni Ribas

IPC: A61K35/17 ,  C07K14/725 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/90

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.