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Enjoy reading! - The SMS-oncology team
Investigators from the University of Pennsylvania have started a first-ever immunotherapy trial in the US using CRISPR-Cas9 cell editing technology. Two patients with relapsed cancers, multiple myeloma and sarcoma, are being treated. In an approach that parallels CART-cell therapy, researchers on genetically modified allogeneic T-cells and infused them into patients that underwent chemotherapy. The scientists aim to knock out wild-type T-cell receptor (TCR) and PD-1 genes, while knock-in NY-ESO-1 TCR genes. NY-ESO-1 is a cancer-testis antigen that is expressed in certain tumor types, being upregulated in half or all breast cancers. With a NY-ESO-1 receptor knock-in, scientists supercharge the T cells to identify and combat cancer cells. Meanwhile, the patients are closely monitored to assess the treatment efficiency and survival rates. The trial is designed to enroll a total of 18 patients, marking small yet laudable steps to unleash CRISPR's potential in the clinic. (Image source: Getty Images)
Throughout the years, researchers have identified the delicate interaction of nerve-tumor cell population and its contribution to cancer progression. In cancer development, similar embryo development, nerves are required for tissue repair and regeneration. However, until now it was unknown how tumor permits the generation of such nerve cells. Recently, Mauffrey et al. Reported findings or a process found in mice called neo-neurogenesis. The study results suggest that a neural progenitor cell could migrate from the Dentate gyrus, a part of the hippocampal formation, to the site of prostate cancer through blood vessels and give rise to neuroblast cells. These neuroblasts express a specific neuronal migration protein called doublecortin (DCX +), which is present in dividing embryonic neurons and is downregulated after 2 weeks. Further analysis revealed that selective DCX + depletion in mice had impaired tumor development, whereas neuroblast transplantation or DCX + from mice with prostate tumors or their neural precursors induced tumorigenesis. In addition, scientists validated that higher numbers of neuroblasts in human prostate samples correlated with greater aggressiveness and recurrence of these tumors. Additional research in different mouse models is needed to characterize the mechanism of neural progenitor cells journey from neurogenic niches to cancer sites. The article was published in Nature. (Image source: Nature)
Recent advancements in cancer detection now allow scientist to perform molecular whole-transcriptome analysis to profile a spectrum of cancer cells from a liquid biopsy of a single patient. Earlier technologies were limited to investigating only a subset of cancer cells or looking into only a number of genes throughout cancer variants. Furthermore, previous methods faced the cumbersome issue of sample contamination and were ineffective to detect scarce numbers of circulating tumor cells (CTCs). CTCs are rare, highly heterogeneous cancer cells involved in the initiation of metastasis and are regarded as promising biomarkers. With the development of a novel Hydro-Seq chip, it is now possible to perform a contamination-free high-throughput single-cell RNA-sequencing (scRNA-seq) of such molecules. The chip allows high size-based single-cell capture efficiency due to pneumatic valves designed for the washing of cellular and acellular contaminants. The bead-cell-pairing chambers with on-chip valves can be scaled up to thousands of chambers for massively parallel analysis compared to conventional single-cell manipulations that are difficult, laborious and result in low-throughput. By employing this noninvasive screening technique, scientists analyzed 666 CTCs from blood biopsies of 21 metastatic breast cancer patients. The results of this study can be used to identify rare CTC subtypes and potential drug targets for hormone and targeted therapies. Future transcriptome analysis as such hold the potential to underline the fundamentals of metastasis and cellular heterogeneity of CTC. The study was published in Nature Communication. (Image Source: Cheng et al., Nature Communications)
- Merck acquires Peloton Therapeutics : Merck (MSD outside of US and Canada) has come to a $ 1.05 billion upfront agreement with privately held Peloton Therapeutics, a clinical-stage biopharmaceutical company focused on cancer treatment. Peloton was expected to issue an IPO before the acquisition. Under the current terms, Peloton's shareholders will receive $ 1.15 billion of payments based on the achievements and sales goals. Company's lead candidate PT2977, an oral HIF-2α inhibitor, is currently in late-stage clinical testing for renal cell carcinoma (RCC).
- Amgen's newest $ 167 million acquisition : The world's largest biotech Amgen agreed to acquire Scandinavian biopharmaceutical company Nuevolution for $ 166.8 million. The Copenhagen based enterprise has developed a unique research platform to scout for small molecules for the treatment of cancer, which are inexpensive to manufacture and can be administered in a form of pills.
- Global Oncology Trends for 2019: IQVIA ™ Institute for Human Data Science released their Global Oncology Trends 2019 study, which highlights immunotherapies as the busiest R&D oncologic pipeline with almost 450 trials of a total of 1,170 oncology clinical trials in 2018. Trials focusing on cancer immunotherapy have increased by 23% compared to 2017 and are estimated to grow to spend of $ 200-230 billion worldwide by 2023
EMA / FDA
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- LysaKare (Arginine / Lysine, Advanced Accelerator Applications) designed to protect the kidneys against radiation and reduce exposure during peptide receptor radionuclide therapy with lutetium ( 177 Lu) oxodotreotide. The amino acids decrease the reabsorption and retention of lutetium oxodotreotide in the kidney tubule.
The FDA granted approval for:
- Bavencio in combination with Inlyta (avelumab with axitinib respectively, Merck and Pfizer) as first-line treatment for patients with advanced RCC. This is the first FDA approval for anti-PD-L1 therapy as part of a combination of regimens for patients with advanced RCC.
- Cyramza (ramucirumab, Eli Lilly) for the treatment of patients with hepatocellular carcinoma (HCC) who have an alpha fetoprotein (AFP) or ≥400 ng / mL and have been treated with sorafenib. In 2015, the monoclonal antibody was approved for the treatment of advanced gastric cancer and metastatic non-small cell lung cancer (mNSCLC).
- Keytruda (pembrolizumab, Merck) as first-line monotherapy for the treatment of patients with stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (tumor proportion score [TPS] ≥ 1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. Clinical results grabbed the highlights of ASCO 2019 with the five-year survival data or NSCLC, which reported a 23.2% survival rate in treatment-naïve patients. Keytruda was also approved as first-line treatment in combination with axitinib for patients with advanced renal cell carcinoma (RCC).
- Piqray (alpelisib, Novartis) used in combination with fulvestrant for the treatment of men and postmenopausal women with hormone receptor positive, human epidermal growth factor receptor 2 (HER2) -negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA -approved test following progression on or after an endocrine-based regimen. The compound is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer.
- Venclexta plus Gazyva (venetoclax with obinutuzumab respectively, Genentech and AbbVie) for treatment of patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The granted approval is considered a breakthrough as many CLL patients are ineligible for intensive chemotherapy-based options
One guideline document from the FDA has been published:
- Reproductive Toxicity Testing and Labeling Recommendations Guidance for Industry : Recommendations in this guideline will assist sponsors to evaluate reproductive toxicity (mainly for effects on embryo-fetal development (EFD)) for oncology pharmaceuticals and to provide advice for product labeling on duration of the contraception following cessation of therapy to minimize potential risk to a developing embryo or fetus. This guidance is intended to facilitate the development of oncology pharmaceuticals while avoiding unnecessary use of animals, in accordance with the 3R (reduce, refine, replace) principles.