Methods and compositions for treating cancer (e.g., ovarian, fallopian tube, uterine, cervical, vaginal, vulvar, or peritoneal cancer) are disclosed. The methods include intermittent administration of a glucocorticoid receptor modulator (GRM), such as a non-steroidal GRM (e.g., relacorilant), which may be orally administered, along with a cancer chemotherapy agent to the patient. The patient may have received bevacizumab prior to receiving such intermittent GRM plus chemotherapy treatment.

The GRM may be administered: at intervals separated by at least one day without GRM administration; by a schedule linked to the cancer chemotherapy schedule (e.g., a weekly chemotherapy regimen); the day of, or the day before, or the day after, chemotherapy administration; by combinations thereof; and/or on other days.

Ovarian cancer patients receiving intermittent relacorilant administration along with nab-paclitaxel administration had improved overall survival, progression free survival, duration of response, and other benefits as compared to patients not receiving relacorilant while receiving nab-paclitaxel.

Compositions and methods for the treatment of viral infections include conjugates containing inhibitors of viral gp120 receptor (e.g., temsavir, BMS-818251, DMJ-ll-121, BNM-IV-147, or analogs thereof) linked to an Fc monomer, an Fc domain, and Fc-binding peptide, an albumin protein, or albumin-binding peptide. In particular, conjugates can be used in the treatment of viral infections (e.g., HIV infections).

Embodiments of immunogens based on the HIV-1 Env fusion peptide and methods of their use and production are disclosed. Nucleic acid molecules encoding the immunogens are also provided. In several embodiments, the immunogens can be used to generate an immune response to HIV-1 Env in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

This disclosure describes fentanyl haptens, a fentanyl hapten-carrier conjugate, methods of making the fentanyl hapten-carrier conjugate, and methods of using the fentanyl hapten-carrier conjugate including, for example, as a prophylactic vaccine to counteract toxicity from exposure to fentanyl, fentanyl derivatives, and fentanyl analogs. In some embodiments, the fentanyl hapten-carrier conjugate or a composition including the fentanyl hapten-carrier conjugate may be used in an anti-opioid vaccine.

The present invention in various aspects and embodiments involves the use of CO releasing molecules, such as conjugates comprising tumour-selective ligands and groups capable of releasing carbon monoxide (CO), for exerting immunomodulatory effects in cancer treatment, such as reductions in the expression of immune checkpoint molecules and the level of inhibitory macrophages. This can reduce immunosuppression in tumour tissue and can be useful, for example, in the treatment of immunosuppressive cancers or the treatment of cancers in combination with cancer immunotherapy.

The present disclosure provides targeted T-cell engaging agents (TEAC) and antibody tumor-targeting assembly complexes (ATTAC) for targeting to cancer. The TEAC or ATTAC described herein may have, for example, longer half-life or comprise multiple components in a single agent.

Disclosed are methods and related compositions for administering a high affinity IL-2 receptor agonist in combination with immunosuppressants. The methods and compositions provided can be used for enhancing regulatory T cells, including antigen-specific regulatory T cells.

In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.

Described herein are methods, formulations and kits for treating a patient with cancer with anti-VEGF antibodies and albumin-bound chemotherapeutic/anti-VEGF antibody nanoparticle complexes.

An improved heroin conjugate vaccine is detailed; to accomplish this task the systematic exploration of twenty vaccine formulations with varying combinations of carrier proteins and adjuvants were undertaken. In regard to adjuvants, a Toll-like receptor 9 (TLR9) agonist and a TLR3 agonist in the presence of alum were explored. The vaccine formulations containing TLR3 or TLR9 agonist alone-elicited strong anti-heroin antibody titers and blockade of heroin-induced antinociception when formulated with alum; however, a combination of TLR3 and 9 adjuvants did not result in improved efficacy. Investigation of stability of the two lead formulations revealed that the TLR9 but not the TLR3 formulation was stable when stored over 30 days. Furthermore, mice immunized with the TLR9+alum heroin vaccine gained significant protection from lethal heroin doses, suggesting that this vaccine formulation is suitable for mitigating the lethal effects of heroin, even following long-term storage at room temperature.