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Adoptive T-cell therapy (ACT) utilizes tumor-reactive T cells to induce disease remission. While ACT has been used effectively to treat metastatic melanoma and certain epithelial cancers, most patients do not respond to treatment. Although the mechanisms underlying this variable response to therapy are not fully elucidated, the phenotype of the adoptively transferred cell is known to be a key determinant of treatment efficacy.

Human immunodeficiency virus (HIV) infections remain a pandemic, most prevalent in Africa and the Americas. Anti-retroviral treatments have been effective in preventing spread of the virus and active outbreaks of acquired immune deficiency syndrome (AIDS). However, the development and deployment of an effective vaccine would provide long-lasting protection and alleviate the need to depend heavily on prevention methods that require continued access and adherence.

One form of adoptive T cell therapy (ACT) consists of harvesting tumor infiltrating lymphocytes (TIL), screening and isolating TIL which display tumor antigen-specific T-cell receptors (TCR), expanding the isolated T cells in vitro, and reinfusing them into the patient for treatment. While highly active in the treatment of certain cancers (e.g., melanoma), current methods used to produce cancer-reactive T cells require significant time and may not adequately identify the desired TCRs which bind cancer targets.

The blood brain barrier (BBB) is a specialized endothelium that prevents the uptake of substances from the systemic circulation into the central nervous system. This barrier, while protecting the sensitive physiological environment of the brain, is also a major impediment in administering therapeutics that need to pass through the BBB. A drug delivery platform that could deliver therapeutic agents directly to the brain is needed, and could have wide ranging significance in a variety of psychiatric, oncology, infectious, and neurodegenerative diseases.

Several viral epidemics – such as the epidemics caused by H1N1 influenza virus, human immunodeficiency virus (HIV), Ebola virus, Zika virus, severe acute respiratory syndrome (SARS) virus, Middle East respiratory syndrome (MERS) virus and SARS-CoV-2 – have profoundly impacted global human health. Early identification of infected and/or infectious persons and isolating them from the population are some of the most effective and evident measures to prevent human-to-human spreading.

Adoptive cell transfer (ACT) uses tumor infiltrating lymphocytes (TILs) that recognize unique antigens expressed by cancer cells (“neoantigens”). Neoantigen specific TIL administration in patients has resulted in long term regression of certain metastatic cancers. However, one of the challenges of ACT and engineered T cell receptor (TCR) therapies more broadly, is the identification and isolation of these mutation specific TILs and TCRs. Only a fraction of TILs in a given patient is known to be tumor reactive, while the majority are not useful for cell therapy.

Adoptive cell transfer (ACT) uses tumor infiltrating lymphocytes (TILs) that recognize antigens expressed by cancer cells (neoantigens). Neoantigen specific TIL administration in patients has resulted in long-term regression of certain metastatic cancers. However, current procedures for TIL therapy are highly invasive, labor-intensive, and time consuming. The success of these procedures is limited and differs between patients and histologies.

CD20 is a protein expressed by wide ranges of lymphoid malignancies originating from B cells but not by indispensable normal tissues, making it an attractive target for therapies such as T-cell receptor (TCR) therapy. Current anti-CD20 therapeutics face a number of limitations. The most important limitation to current anti-CD20 therapies include cancer cells becoming resistant to the therapy.

Pancreatic ductal adenocarcinoma (PDA) accounts for more than 90% of pancreatic cancer cases, and it is one of the most aggressive malignancies with a 5-year survival rate of 6%. The high mortality rate caused by PDA is primarily from the lack of early diagnosis – it is often asymptomatic in early stages – and a poor response to conventional chemotherapy and radiotherapy. One of the major immune cell types present in the PDA microenvironment is a subset of macrophages commonly termed tumor-associated macrophages (TAM).

Gammaretroviral vectors were the first viral gene-therapy vectors to enter clinical trials and remain in use. One potential hazard associated with the use of such vectors is the presence of replication-competent retroviruses (RCR) in the vector preparations – either as a result of: 1) recombination events between the plasmids used for vector production, 2) interactions between the plasmids and endogenous retroviral sequences in the packaging cell lines, or 3) as a result of contamination in the laboratory.