The results of CheckMate 214 demonstrated that combination checkpoint immunotherapy with nivolumab (Opdivo; anti-PD-1 monoclonal antibody) and ipilimumab (Yervoy; anti-CTLA-4 monoclonal antibody), is superior to sunitinib (Sutent; multikinase inhibitor) in the treatment of patients with newly diagnosed renal cell carcinoma (RCC). Interestingly, prior to sunitinib, another immunotherapeutic approach – interferon-alpha (IFN-α) – was the front-line treatment of choice for renal cell carcinoma, which, like melanoma, is very immune-responsive. Continue reading
Author Archives: Joseph Gulfo
New Link’s Indoximod + Keytruda looks promising in Phase 2 advanced melanoma
Indoximod + Keytruda looks promising in Phase 2 advanced melanoma
IDO (indoleamine-2,3-dioxygenase) is an intracellular enzyme found in antigen presenting cells that mediates immune suppression in the tumor microenvironment. Continue reading
WP1122 is a 2-deoxy-D-glucose prodrug in pre-clinical development for glioblastoma
The Warburg Effect is a universal feature of cancer; it describes the phenomenon whereby cancer cells preferentially use glucose for anaerobic glycolysis, as opposed to aerobic respiration via the Krebs Cycle. In order to meet the increased energy demands using a much less efficient process for ATP production, cancer cells take-up 20-times more glucose than wild-type cells. Continue reading
OLIG2 inhibitor for glioblastoma
OLIG2 (Oligodendrocyte transcription factor-2) is a transcription factor that is expressed in the pMN domain of the ventral ventricular zone in the embryonic spinal cord. Along with OLIG1, it is responsible for the development of motoneurons and oligodendrocytes. Astrocytes and ependymal cells also originate from the pMN domain. Continue reading
Recent immune checkpoint study failures do not dampen enthusiasm for the future
Immune checkpoint inhibitors are simply cancer wonder drugs about which we are learning more each day. Because they don’t work optimally in many patients and some even hyper-progress, the goal is to determine ways to expand their effectiveness to more patients. As such, the number of clinical studies with checkpoints and checkpoint combinations continues to grow.
Immune checkpoint inhibitors act by blocking the abrogating phase of the immune response that is necessary to prevent autoimmune disease – by prolonging the immune response against cancer, a more robust and prolonged immune response, which is required for effective cancer therapy, is achieved with checkpoint therapy. Continue reading
Sellas merges with Galena to advance WT1 peptide cancer vaccine
Sellas reversed merged into Galena, a peptide vaccine company whose lead product, NeuVax, for breast cancer failed. Sellas’ lead product is galinpepimut-S for AML (acute myelogenous leukemia) and mesothelioma, as well as other cancers. Continue reading
NLRP3 and STING enhance immune attack on cancer
Bristol Myers (BMS) acquired IFM Therapeutics for $300 MM up-front and up to $1.01 billion in contingent payments on the first two products from the NLRP and STING (STimulator of INterferon Genes) pre-clinical programs. IFM focuses on the innate immune system, which is the first line of immunological defense, whereas, BMS’ immune-oncology program (most notably featuring Yervoy and Opdivo, checkpoint inhibitors of CTLA4 and PD-1) has largely centered on the adaptive immune system. IFM is developing small molecule agonists that target the innate immune response within the tumor microenvironment. Continue reading
ALK-positive lung cancer – antibodies to fusion protein
Approximately 7% of patients with non-small cell lung cancer (NSCLC) possess a transgene that results from an inversion of chromosome 2 that juxtaposes the 5’ end of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the 3′ end of the anaplastic lymphoma kinase (ALK) gene, resulting in the novel fusion oncogene EML4-ALK . Continue reading
MDM2 and MDMX inhibitor restores p53 functioning in cancers with wild-type p53
P53 is a tumor suppressor gene that pauses cell division to allow for repair of gene damage, and triggers apoptosis if the damage is not reparable. Loss of p53 is a critical step in the evolution of cancer. Most frequently, p53 is mutated at its DNA binding domain; since p53 is a transcription factor, a diminished ability to bind to DNA significantly disrupts its functioning. Continue reading
CD-19 CAR T-cell gets unanimous ODAC recommendation and Blincyto wins full FDA approval – managing cytokine release syndrome
This week, the FDA Oncology Drug Advisory Committee provided a unanimous recommendation to Novartis’ tisagenlecleucel, a CAR (chimeric antigen receptor) T-cell therapy directed against CD19 for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). In addition, the FDA granted full approval to Amgen for Blincyto (blinatumomab), a bispecific monoclonal antibody that targets CD19, for indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children. Blincyto received conditional approval in 2015 for this claim. Continue reading