The Johns Hopkins University

Ivan M Borrello

Kimberly A Noonan

Hyam I Levitsky

Richard F Ambinder

Yiping Yang

Drew M Pardoll

Paolo Serafini

Vincenzo Bronte

Valentina Hoyos Velez

In some embodiments, marrow-infiltrating lymphocytes ('MILs') comprising a chimeric antigen receptor ('CAR') are provided. In some aspects, the embodiments relate to a method for making a recombinant MIL, comprising obtaining bone marrow comprising MILs; and transfecting, transforming, or transducing the MILs with a nucleic acid encoding a chimeric antigen receptor. In some aspects, the embodiments relate to a method for treating a condition in a subject, comprising administering to the subject a MIL comprising a CAR.

Marrow infiltrating lymphocytes (MILs) as a source of T-cells for chimeric antigen receptor (CAR) therapy

In some aspects, the invention relates to compositions comprising marrow infiltrating lymphocytes ('MILs'). The MILs may be activated MILs. In some aspects, the invention relates to methods for activating MILs, comprising incubating MILs in an environment comprising less than 21% oxygen. In some aspects, the invention relates to methods for treating cancer in a subject, comprising administering to the subject a composition comprising activated MILs.

Activation of marrow infiltrating lymphocytes in hypoxic alternating with normoxic conditions

Various embodiments of the invention relate to compositions comprising marrow infiltrating lymphocytes ('MILs'). The MILs may be activated MILs. Some embodiments relate to methods for activating MILs, comprising incubating MILs in an environment comprising less than 21% oxygen. Some embodiments relate to methods for treating cancer in a subject, comprising administering to the subject a composition comprising activated MILs.

The invention features methods and compositions featuring a PDE5 inhibitor for treating or preventing immunological-mediated disease in a subject.

PDE5 inhibitor compositions and methods for immunotherapy

A human cell line, which lacks major histocompatibility class I (MHC-I) antigens and major histocompatibility class II (MHC-II) antigens and which has been modified to comprise and express (i) a nucleotide sequence encoding an immunomodulator and (ii) a nucleotide sequence encoding a viral antigen, and a method of inducing or stimulating an immune response in a human to a viral-associated disease or cancer comprising administering to the human (i) the aforementioned human cell line in an amount sufficient to induce or stimulate an immune response to the viral associated disease or cancer, (ii) a human cell line, which lacks MHC-I and MHC-11 antigens and which has been modified to comprise and express a nucleotide sequence encoding an immunomodulator, and a human cell line, which lacks MHC-I and MHC-II antigens and which has been modified to comprise and express a nucleotide sequence encoding an antigen of EBV, simultaneously or sequentially in either order, by the same or different routes, in amounts sufficient to induce or stimulate an immune response to the viral-associated disease or cancer, or (iii) an immunomodulator and a human cell line, which lacks MHC-I and MHC-II antigens and which has been modified to comprise and express a nucleotide sequence encoding an antigen of EBV, simultaneously or sequentially in either order, by the same or different routes, in amounts sufficient to induce or stimulate an immune response to the viral associated disease or cancer.

Cancer immunotherapy with a viral antigen-defined, immunomodulator-secreting cell vaccine

The present invention provides a universal immunomodulatory cytokine-expressing bystander cell line, a composition comprising such a cell line and a cancer antigen, a method of making such a cell line, and a method of using such a composition.

Universal GM-CSF expressing bystander human K562 cell line

The present invention provides a universal immunomodulatory cytokine-expressing bystander cell line, a composition comprising such a cell line cancer antigen, a method of making such a cell line, and a method of using such a composition.

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Baltimore, MD, United States of America

Ivan M Borrello