The present invention relates to novel prime-boost regimens that involve the administration of at least one mRNA construct, such as the use of such constructs in “boost” administration subsequently to “prime” administration of certain other antigenic composition(s). Such inventive regimens may, in particular, be useful for the induction of an immune response in a subject, and/or the vaccination of such subject against infection from one or more pathogens, and/or the treatment or prevention of one or more diseases or conditions, including a tumour or cancer, allergy or autoimmune conditions, and/or a disease or condition associated with infection from a pathogen. The present invention further describes methods, uses, vaccination compositions, kits and packaged vaccine components related to or useful for one or more of such regimens

In some embodiments, marrow-infiltrating lymphocytes (“MILs”) comprising a chimeric antigen receptor (“CAR”) are provided. In some aspects, the embodiments relate to a MIL obtained from bone marrow comprising 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.

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Provided herein are methods of treating graft-versus-host disease in a subject by administering pharmaceutical compositions containing bacterial strains of the Clostridia class. Also described herein are exemplary human-derived bacteria belonging to the Clostridia class, combinations of which have been shown to induce accumulation of regulatory T cells (Treg cells) in the colon and suppress immune functions, and are therefore useful for mitigating pathological immune responses. Pharmaceutical compositions containing these and/or related bacteria can be used to prevent and treat immune-mediated diseases such as graft-versus-host disease.

The invention relates generally to polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator (uPA), to activatable antibodies and other larger molecules that include the cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator, and to methods of making and using these polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator in a variety of therapeutic, diagnostic and prophylactic indications.

The present invention relates to immunoglobulin single variable domains that bind GITR and more in particular to polypeptides that comprise or essentially consist of one or more such immunoglobulin single variable domains; to nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the polypeptides of the present invention enhance the biological activity of GITR.

The present disclosure provides antibody drug conjugates comprising STING modulators. Also provided are compositions comprising the antibody drug conjugates. The compounds and compositions are useful for stimulating an immune response in a subject in need thereof. Formula (I):

##STR00001##

Provided herein are macrolide compounds of Formula (I) and (I-N) for the treatment of infectious diseases and inflammatory conditions. The 14-membered ketolides and 14-, 15-, and 16-membered azaketolides described herein comprise modified sugars which are desosamine or mycaminose analogs. Pharmaceutical compositions and methods of treating infection diseases and inflammatory conditions using the inventive macrolides are also provided. This disclosure additionally provides methods of preparing the macrolides by the coupling of an eastern and western half. ##STR00001##

The present invention relates to nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.

The present invention relates to methods and materials for modulating the complement alternative pathway (CAP), the complement classical pathway (CCP), the complement lectin/mannose pathway (CMP), or combinations thereof, as well as methods and materials for targeting diagnostic, prophylactic and therapeutic agents to localized areas of tissue within the body where they may more directly exert their effects upon the intended target cells or tissue, with reduced, associated systemic effects compared with administration of the same or similar agents in an untargeted, systemic manner. The methods and materials of the present invention may therefore allow for increased efficacy, lower threshold effective dosages and/or lower effective maintenance doses, and/or reduced associated undesired or adverse effects in terms of frequency or severity of occurrence, or both. The present invention also relates to methods and materials for modulating a host humoral immune response, especially reducing, inhibiting, or preventing a host humoral immune response.