公开(公告)号：US20240100160A1

公开(公告)日：2024-03-28

申请号：US18475042

申请日：2023-09-26

申请人： Regen Biopharma, Inc.

发明人： Thomas ICHIM ,  Harry LANDER ,  David KOOS

IPC分类号： A61K39/00 ,  C07K14/725 ,  C12N5/0783

CPC分类号： A61K39/4632 ,  A61K39/4611 ,  C07K14/7051 ,  C12N5/0636 ,  A61K2239/28 ,  C12N2510/00

摘要： Disclosed are means, methods and compositions of matter useful for stimulation enhancement of T cell homing into tumors and overcoming tumor microenvironment. In one embodiment the invention provides an engineered T cell in which engagement of T cell receptor on said T cell results in upregulation of T cell attracting chemokines so as to induce an increased proportion of T cells to tumor cells. In another embodiment, T cell chemokine secreting cells are administrated intratumorally in order to augment T cell infiltration into said tumors. In other embodiments administration of lymphopoietic cytokines is performed intratumorally to enhance viability of T cells approaching and residing in the microenvironment. Combinations of agents which counteract tumor microenvironment induced immune suppression are also disclosed.

公开(公告)号：US20240066126A1

公开(公告)日：2024-02-29

申请号：US18455544

申请日：2023-08-24

申请人： Regen Biopharma, Inc.

发明人： Thomas ICHIM ,  David KOOS ,  Harry LANDER

IPC分类号： A61K39/00 ,  A61K38/17 ,  A61K38/19

CPC分类号： A61K39/4631 ,  A61K38/1725 ,  A61K38/193 ,  A61K39/4614

摘要： Disclosed are combination therapies for cancer utilizing the leverage of the adaptive immune system through chimeric antigen receptor (CAR) T cells, combined with leveraging the innate immune system by using CAR-macrophages (CAR-M) and CAR-natural killer (NK) cells. In some embodiments, the invention teaches the initial modification of the tumor microenvironment by administration of CAR-M and CAR-NK. The alteration of the tumor microenvironment results in reduction of barriers for CAR-T cells to enter the tumor, which allows for efficacy of CAR-T in treatment of solid tumors. In some embodiments adjuvant immunotherapies are utilized to expand immunological attack such as addition of complement, immunotherapeutic antibodies, chemotherapy and radiotherapy approaches.

公开(公告)号：US20170362596A1

公开(公告)日：2017-12-21

申请号：US15431681

申请日：2017-02-13

申请人： Regen Biopharma, Inc

发明人： David KOOS ,  Thomas ICHIM ,  Santosh KESARI

IPC分类号： C12N15/113 ,  A61K35/17 ,  C12N5/0783

CPC分类号： C12N15/1138 ,  A61K35/17 ,  C12N5/0638 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/3341 ,  C12N2501/60 ,  C12N2502/1157

摘要： Disclosed are means, methods, and compositions of matter useful for generation of cancer inhibitory effector cells producing interleukin-17 (IL-17). In one embodiment a cellular population is obtained, said cellular population is exposed to agents capable of inhibiting NR2F6, whereby said inhibition of NR2F6 results in upregulation of IL-17 production, said upregulation of IL-17 production associated with acquisition of anti-tumor activity.

公开(公告)号：US20170166896A1

公开(公告)日：2017-06-15

申请号：US15250877

申请日：2016-08-29

申请人： Regen Biopharma, Inc

发明人： David Koos ,  Thomas ICHIM

IPC分类号： C12N15/113 ,  A61K47/18 ,  A61K45/06 ,  A61K31/713

CPC分类号： C12N15/1136 ,  A61K31/713 ,  A61K33/18 ,  A61K45/06 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/531 ,  C12N2320/31 ,  C12N2320/32 ,  A61K2300/00

摘要： Methods of treatment of cancer are disclosed through administration of siRNA and shRNA sequences silencing BORIS gene and isoforms thereof. One embodiment of the invention discloses pharmaceutical compositions and kits for modifying the palliative procedure of transarterial chemoembolization so as to promote uptake of gene silencing inducing agents into the hepatic cancer microenvironment. By selectively administering under localized increased pressure, enhanced uptake of gene silencing agents is achieved, thus increasing targeting of tumor cells, particularly stem cells.

公开(公告)号：US20240165204A1

公开(公告)日：2024-05-23

申请号：US18516884

申请日：2023-11-21

申请人： Regen Biopharma, Inc.

发明人： Thomas ICHIM ,  Harry LANDER ,  David KOOS

IPC分类号： A61K38/21 ,  A61K31/166 ,  A61K31/192 ,  A61P35/00

CPC分类号： A61K38/217 ,  A61K31/166 ,  A61K31/192 ,  A61P35/00

摘要： Disclosed are compositions of matter and therapeutic means for increasing efficacy of immunotherapy such as Tumor Infiltrating Lymphocytes (TILs), Chimeric Antigen Receptor (CAR)-T cells, and other cellular therapies in solid tumors. In one embodiment agents capable of increasing tumor immunogenicity and/or antigen presentation by modulation of tumor stromal cells such as monocytes and pericytes are administered prior to providing immunotherapy in a patient. In some embodiments administration of interleukin-33 together with one or more antioxidants is provided as a means of stimulating expression of HLA and TAP proteins without inducing significant inflammatory response and myeloid derived suppressor cell activation in cancer associated monocytes. In other embodiments the use of histone deacetylase (HDAC) inhibitors together with interferon alpha is disclosed as a means of stimulating the expression of immunogenic molecules on monocytes to increase immunotherapy cell activity.

公开(公告)号：US20170246207A1

公开(公告)日：2017-08-31

申请号：US15162370

申请日：2016-05-23

申请人： Regen Biopharma, Inc

发明人： David KOOS ,  Thomas ICHIM

IPC分类号： A61K35/15

CPC分类号： A61K35/15 ,  A61K38/10 ,  A61K38/16

摘要： Disclosed are antigen specific cancer vaccines in which immunogenic epitopes are produced intracellularly by administration of modified mRNA encoding said immunogenic epitopes. In one embodiment of the invention, said modified mRNA encodes peptides derived from the protein survivin. By directly inducing gene expression of the antigens to which an immune response is desired, immunogenic peptides are generated intracellularly, thus allowing for a wider repertoire of epitopes to be presented to the adaptive immune system, which augments likelihood of successful induction of immunity.

公开(公告)号：US20240093205A1

公开(公告)日：2024-03-21

申请号：US18470300

申请日：2023-09-19

申请人： Regen Biopharma, Inc.

发明人： Thomas ICHIM ,  David KOOS ,  Harry LANDER

IPC分类号： C12N15/115

CPC分类号： C12N15/115 ,  C12N2310/16 ,  C12N2310/531

摘要： Disclosed are aptamers designed to bind immunological checkpoint molecules while concurrently suppressing tumor associated gene expression through delivery of DNA molecules encoding short hairpin DNA. In one embodiment the invention provides an aptamer capable of binding PD-1 and/or PD-1 ligand while concurrently possessing ability to induce RNA interference to one more multiple other immune inhibitory and/or oncogenesis related genes. In one embodiment such a dual-targeting aptamer is utilized to induce systemic tumor abscopal effect.

公开(公告)号：US20240024443A1

公开(公告)日：2024-01-25

申请号：US18358432

申请日：2023-07-25

申请人： Regen Biopharma, Inc.

发明人： Thomas ICHIM ,  David KOOS

IPC分类号： A61K39/00

CPC分类号： A61K39/00115 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/55522 ,  A61K2039/55527 ,  A61K2039/55516 ,  A61K2039/55533

摘要： Disclosed are methods, and compositions useful for stimulation of immunity towards cancer by utilizing dendritic cells and products therefrom that have been stimulated and/or incorporated mRNA encoding survivin and/or related gene sequences, defined herein as “survivin modified mRNA”. In one embodiment dendritic cells generated from allogeneic “off the shelf” sources are transfected with survivin modified mRNA and the cells are administered in an immunogenic manner. In some embodiments transfected dendritic cells are induced to undergo immunogenic cell death ex vivo subsequently to which they are used as immunogenic stimuli. In other embodiments preparation of the injection site is performed prior to administration of dendritic cells that have been transfected with survivin modified mRNA by pre-administration of agents increasing the number of local dendritic cells in the skin. In embodiments in vivo, transfection of survivin modified mRNA is performed by administration of dendritic cell accumulating agents followed by in vivo transfection.