Lysosomal processing of sulfatide analogs alters target NKT cell specificity and immune responses in cancer.

In a structure-function study of sulfatides that typically stimulate type II NKT cells, we made an unexpected discovery. We compared analogs with sphingosine or phytosphingosine chains and 24-carbon acyl chains with 0-1-2 double bonds (C or pC24:0, 24:1, or 24:2). C24:1 and C24:2 sulfatide presented by the CD1d monomer on plastic stimulated type II, not type I, NKT cell hybridomas, as expected.

BCMA-targeted immunotherapy for multiple myeloma.

B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM.

Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory.

The benefits of anti-cancer agents extend beyond direct tumor killing. One aspect of cell death is the potential to release antigens that initiate adaptive immune responses. Here, a diffusion enhanced formulation, INT230-6, containing potent anti-cancer cytotoxic agents, was administered intratumorally into large (approx.

A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells.

Recently, interactions between thrombopoietin (TPO) and its receptor, the myeloproliferative leukemia (MPL) virus oncogene, have been shown to play a role in the development and progression of myeloproliferative neoplasms including myelofibrosis (MF). These observations have led to the development of strategies to disrupt the association of TPO with its receptor as a means of targeting MF hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). In this report, we show that although both splenic and peripheral blood MF CD34(+) cells expressed lower levels of MPL than normal CD34(+) cells, TPO promoted the proliferation of MF CD34(+) cells and HPCs in a dose-dependent fashion.