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.
Recombinant Immunotoxins (RITs) are chimeric molecules composed of an antigen binding domain and toxin. The antigen binding domain component targets the cancer cell and delivers the toxin component to the cell. However, the efficacy of RITs is limited by their short half-life once they are in the patient. To address this problem, investigators at the National Cancer Institute (NCI) increased the half-life of RITs using polyethylene glycol (PEG).
Mesothelin (MSLN) is an antigen highly expressed in several human cancers including mesotheliomas, ovarian cancers and pancreatic cancers. As such, human MSLN (hMSLN) is a target for many anti-cancer drugs. Most therapeutics targeting hMSLN do not recognize the mouse isoform of MSLN (mMSLN) and therefore cannot be tested in mouse cancer models.
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).
CD276 (also called B7-H3) is a pan-cancer antigen expressed in multiple solid tumors and an emerging cancer target. CD276 protein is overexpressed in pancreatic cancer, prostate cancer, breast cancer, colon cancer, lung cancer, and brain tumors (such as neuroblastoma) – making it an ideal target for cancer therapy.
Investigators at the National Cancer Institute (NCI) have isolated a panel of anti-CD276 single domain antibodies (also known as nanobodies) from novel camel and rabbit single domain (VHH) libraries by phage display.
Advanced stage cancers are typically marked by metastases of the primary cancer to secondary sites such as lungs, liver, and bones. Such metastatic cancers result in strikingly low 5-year survival rates, underscoring the need for novel therapeutics. For example, bone metastasis of primary breast cancer has a 5-year survival rate of 13%, lung cancer only 1%. There is a need for targeted therapy options specific to metastases. One approach to targeting metastases is to reduce cancer cell migration and invasion.
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.
Prostate cancer is the most prevalent form of cancer among all men in the United States (US). It is also the second leading cause of cancer-related deaths in the US among men, largely due to the progressively treatment resistant nature of the disease. Treatment options for early stage prostate cancer include watchful waiting, radical prostatectomy, radiation therapy, and importantly androgen-deprivation therapy (ADT). Prostate cancer is dependent on androgen hormones, such as testosterone, for sustaining and promoting growth.
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL), T cell receptor (TCR) and Chimeric Antigen Receptor (CAR) engineered T cells, or hematopoietic stem cell transplantation, is a promising new approach to cancer treatment. ACT harnesses an individual's adaptive immune system to fight against cancer, with fewer side-effects and more specific anti-tumor activity. Despite their promise of ACT as curative, these therapies are often limited by the persistence and robustness of the responses of the T cells to the cancer cells.
Cancer diagnosis is based on the assessment of patient biopsies to determine the tumor type, grade, and stage of malignancy. The proliferative potential of tumors correlates to their growth and metastasis. Visually identifying and quantifying mitotic figures (MF) in cancer biopsy tissue can be used as a surrogate for proliferative activity in tumors.