Massachusetts Institute of Technology

The Scripps Research Institute

Sanofi Pasteur Vaxdesign Corporation

Harvard College

The Ohio State University

Whitehead Institute for Biomedical Research

Mount Sinai School of Medicine

Janssen Vaccines & Prevention B.v.

La Jolla Institute for Immunology

Leland Stanford Junior University

The General Hospital Corporation

Kyoto University

Imperial College Innovations Limited

Vaxdesign Corporation

New York University

Darrell J Irvine

Jaehyun Moon

Karl Dane Wittrup

Ron Weiss

Li Tang

William L Warren

Russell Higbee

Heather Fahlenkamp

Guzman Sanchez-Schmitz

Mariane Bandeira Melo

Anatoly Kachurin

Conan Li

Robert Parkhill

Mike Nguyen

Gwendalyn J Randolph

Haipeng Liu

Tasuku Kitada

Yingzhong Li

Tyson Moyer

Bruce Torbett

Paula T Hammond

Linda G Griffith

Anne M Mayes

Pallab Banerjee

Kelly Dare Moynihan

Terry D Johnson

Klavs F Jensen

Ronald Vogels

Ulrich Von Andrian

Nir Hacohen

Bradley Lether Pentelute

Yizhou Dong

Pamela A Basto

Armon R Sharei

Ely Blanton Porter

Shane Crotty

Matthias Stephan

Siddharth Jhunjhunwala

Rebecca Lynn Holden

Marijn Van Der Neut Kolfschoten

Noor Momin

Gregory Lee Szeto

Eric Dane

Shirley Mao

George Hartoularos

Anna Bershteyn

Sophia Liu

Nir Harcohen

Megan Heimann

Antonio Eric Barberio

Santiago Correa Echavarria

Talar Tokatlian

Erik Christopher Dreaden

Murillo Silva

Yash Agarwal

Yiran Zheng

Chensu Wang

Robert Samuel Langer

Sangeeta N Bhatia

Jennifer R Cochran

Robert E Cohen

Michael F Rubner

Hirohide Saito

Donald Drake

William Ray Schief

Joel Voldman

Robert S Langer, Jr

Bruce D Walker

Mark Bathe

Andrew Warren

Albert Joseph Swiston

Kei Endo

Yuan Zhang

Jaideep S Dudani

Peter C Demuth

Byron Hua Kwan

John Christopher Love

Remi Veneziano

Richard Bradley Jones

Liliana Wroblewska

Maria Hottelet Foley

Eike-Christian Wamhoff

Benjamin Joseph Read

Velia Siciliano

Naveen K Mehta

Yu Kato

Cary Francis Opel

Sylvain Ladame

Leyuan Ma

Gregory Szeto

Benjamin Cossette

Naveen Mehta

Jan Lonzaric

Dana Al Sulaiman

Katie Bodner

Parisa Yousefpour

Marc Castellarnau

Tyler Wagner

Jacob Becraft

Provided herein are methods for stimulating an immune response to a target cell population or a target tissue in a subject by administering to the subject a composition comprising an amphiphilic ligand conjugate. Such an amphiphilic ligand conjugate can comprise a lipid, one or more cargos (e.g., a CAR ligand, a chimeric cytokine receptor target, a chimeric co-stimulation receptor target, a synNotch receptor target), and optionally a linker.

Uses of amphiphiles in immune cell therapy and compositions therefor

The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

Immunomodulatory fusion protein-metal hydroxide complexes and methods thereof

The disclosure features chimeric antigen receptor (CAR) ligands, methods for making the same, and immunomodulatory compositions comprising the CAR ligands. The disclosure also features compositions and methods of using the immunomodulatory compositions, for example, to stimulate activation of CAR expressing cells.

Methods of activating anti-CD19 chimeric antigen receptor (CAR) T cells using amphiphilic ligand conjugates comprising CAR-targeting protein sequence motifs

A method and device for preferentially delivering a compound such as an antigen to the cytosol of an immune cell. The method comprises passing a cell suspension comprising the target immune cell through a microfluidic device and contacting the suspension with the compound(s) or payload to be delivered.

Delivery of biomolecules to immune cells

The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Synthetic oncolytic LNP-replicon RNA and uses for cancer immunotherapy

Lipid conjugates for enhanced delivery of cargo to the lymph nodes are disclosed. The lipid conjugates typically include three domains: a lipophilic domain that binds to albumin, a polar block domain, and a cargo such as a molecular adjuvant or immunostimulatory compound (such as an oligonucleotide) or antigenic peptide. Depending on the cargo, the length and compositions of the polar block can be tailored to push the equilibrium toward albumin binding, stable micelle formation, or cell insertion. The conjugates can be administered to a subject, for example, a subject with cancer or an infection, to induce or enhance a robust immune response in the subject.

Immunostimulatory compositions and methods of use thereof

The present disclosure provides a method of treating cancer with a priming dose of combination immunotherapy comprising IL-2 (e.g., extended-PK IL-2), an immune checkpoint inhibitor, a tumor targeting antibody or integrin-binding polypeptide, and optional cancer vaccine, administered prior to maintenance doses of immune checkpoint inhibitor therapy. The methods of the disclosure can be used to treat a broad range of cancer types.

Combination immunotherapy for treatment of melanoma, colon or non-small cell lung cancers

The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.

Methods for in vitro evolution of constructs derived from viruses

Non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided.

Nanoparticle vaccine adjuvant and methods of use thereof

Genetic circuits have been developed to regulate behaviors of replicon RNA in responses to small molecules, which has broader applications, such as for quantitative expression of cargo genes, temporary expression of immunomodulatory cytokines or antigens for better cancer immunotherapy or vaccination, and for increased safety in use of self-replicating vectors or in combination with other viral-delivery vectors. Described herein are genetic circuits suitable for systems that either require a tight off state or a slow off state, which can serve for instance where either a kill switch or prolonged protein expression (e.g., of vaccine antigens) are needed.

Control of replication and transcription of self-replicating RNA in response to small molecules

The present disclosure relates to a device, comprising a base and a plurality of microneedles attached to the base, wherein each microneedle has an outer surface; the outer surface of at least one microneedle being coated with a composition comprising at least one polymer and least one Peptide Nucleic Acid (PNA). The present disclosure additionally relates to a method of detecting an analyte in interstitial fluid (ISF), comprising contacting the device to a subject, for example, to human skin.

Peptide nucleic acid functionalized hydrogel microneedles for sampling and detection of interstitial fluid nucleic acids

Disclosed are particles for delivering cytokinese, such as IL-12, for the treatment of cancer. The particles comprise cytokines non-covalently bound to liposomes, where the liposomes are coated with polyelectrolytes.

Layer-by-layer nanoparticles for cytokine therapy in cancer treatment

Compositions and methods are described for inducing an immune response against an immunogen in humans. The induced immune response is obtained by administering a heterologous prime-boost combination of an in vitro transcribed (IVT) self-replicating RNA (repRNA) and an adenovirus vector. The compositions and methods can be used to provide a protective immunity against a disease, such as a viral infection or a cancer, in humans.

Methods and compositions for heterologous repRNA immunizations

The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.

Albumin binding peptide conjugates and methods thereof

Growing community of inventors

Arlington, MA, United States of America

Darrell J Irvine