Use of Cucurbitacins and Withanolides for the Treatment of Cancer

Certain members of the cucurbitacin and Withanolide family have been identified that can sensitize some tumor cell lines to cell death (apoptosis) on subsequent exposure of the cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL "death receptors". These PARAS include TRAIL itself, and agonist antibodies to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death receptor 5 (DR5, TRAIL-R2). 

Improved CD22 Binders for Effective Immunotherapy Against Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Targeting the CD22 receptor of B-cells with chimeric antigen receptor (CAR)-T cells has been a promising new therapy to treat B-cell malignancies in clinical trials, inducing remission in 70% of patients with relapsed acute lymphoblastic leukemia (ALL). However, diminished CD22 expression on B-cell surface can lead to relapse and decreased remission duration, which may be prevented through increasing CAR-T affinity towards CD22. 

Peptide Mimetic Ligands of Polo-like Kinase 1 Polo Box Domain (“Plk1 PBD Portfolio”)

Polo-like kinase 1 (Plk1) is a critical protein involved in regulation of mitosis, and aberrant expression of this kinase is found in various cancer types.  Inhibition of Plk1 is currently being pursued in pre-clinical drug development for novel anti-cancer therapeutics.  Plk1 contains an allosteric domain, known as the polo-box domain (PBD), that is responsible for localizing the kinase domain to mitotic structures through protein-protein interactions.  

Analogues of Withanolide E Sensitize Cancer Cells Toward Apoptosis

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) protein has been a target of interest in cancer therapy because it plays a large role in inducing cell apoptosis in cancer cells but not in normal cells.  Although TRAIL has been reported to successfully target certain tumor cells which are resistant to traditional chemotherapy or radiation, TRAIL resistance has also been widely observed.  Similarly, Toll-like receptor (TLR) 3 ligands such as poly I:C have also been reported to promote apoptosis in certain cancer cells, though the apoptotic signaling in most

Tni-FNL: An Improved Trichoplusia Ni Cell Line for Protein Expression

Researchers at the National Cancer Institute (NCI) have developed an improved insect cell line, Tni-FNL, derived from the cabbage looper, Trichoplusia ni.  The Tni-FNL cell line is capable of high level expression of heterologous proteins using baculovirus-based expression systems.  When compared to commercially available cell lines used for the same purpose, the Tni-FNL cell line often outperforms those for protein expression.  These cells have a high growth rate and are capable of growth at a lower temperature.

Use of Heterodimeric IL-15 in Adoptive Cell Transfer

Adoptive cell transfer (ACT) is a promising immunotherapeutic approach for cancer treatment. During ACT, if a patient is subjected to lymphodepletion prior to cell transfer, there is an observed improvement in a patient’s response to treatment. However, lymphodepletion is associated with detrimental effects, including severe immune dysfunction that persists after treatment.