Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

Provided herein are dimeric IL-7-Fc fusion proteins that include Fc domains and one or more IL-7s. Also provided herein are variant IL-7s with modifications to reduce heterogeneity and/or reduced affinity/potency. Such variant IL-7s are useful, for example, in the subject dimeric IL-7-Fc fusion proteins. The dimeric IL-7-Fc fusion proteins can be used for applications where increased IL-7 activity is useful, for example, for increasing the proliferation of lymphocyte populations in mounting an anti-tumor response in a subject in need thereof.

The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

The present disclosure relates to methods of treating a cancer (or a tumor) with an IL-7 protein in combination with a multispecific (e.g., bispecific) antibody.

Multifunctional molecules that include i) an antigen binding domain that binds to CD33; and one or both of: an immune cell engager (e.g., chosen from a T cell engager, an NK cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager) or a cytokine molecule. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

Provided herein are anaplastic lymphoma kinase chimeric antigen receptors (ALK CARs). The invention also provides polynucleotides encoding ALK CARs, engineered immune cells comprising an ALK CAR, pharmaceutical compositions thereof, and kits for administering the same. Methods of treating a subject with a disease by administering the ALK CAR or engineered immune cell comprising an ALK CAR, or pharmaceutical compositions thereof, are also provided.

The present invention relates to pseudotyped retrovirus-like particles or retroviral vectors comprising both engineered envelope glycoproteins derived from a virus of the Paramyxoviridae family fused to a cell targeting domain and fused to a functional domain. The present invention also relates to the use of said pseudotyped retrovirus-like particles or retroviral vectors to selectively modulate the activity of specific subsets of cells, in particular of specific immune cells. These pseudotyped retrovirus-like particles or retroviral vectors are particularly useful for gene therapy, immune therapy and/or vaccination.

Provided herein are multi-chain chimeric polypeptides that include:

(a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

Embodiments relate to peptide antagonists of γc-family cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting γc-cytokine activity involve raising neutralizing antibodies against each individual γc-cytokine family member/receptor subunit. However, success has been limited and often multiple γc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.

The present invention relates to high-titer hybrid vims vectors which produce virus-like vesicle (VLVs) and compositions and methods thereof for targeting a malignancy or infectious disease. VLVs are a capsid-free, self-replicating artificial virus platform carrying positive-strand capped and polyadenylated RNA encoding an in vitro evolved Semliki Forest vims (SFV) RNA-dependent RNA replicase and the vesicular stomatitis virus (VSV) glycoprotein. The VLVs of the present invention and pharmaceutical compositions thereof encode for polynucleotide and/or polypeptide therapeutic agents useful in methods for the treatment, prophylaxis, and prevention of malignancies and infectious diseases.