Argos, Agenus tumor vaccine both fall
Release date: 2017-02-24
news
Today, a phase III clinical trial of the Argos kidney cancer vaccine rocapuldencel-T combined with the targeted therapy Sutent is expected to be terminated early because of the efficacy that is beyond Sutent's recommendation by the external panel. Previously, the technology has failed in the AIDS clinical trial, so today's repeated mistakes have caused many people to question the feasibility of this technology. On the same day, another immunotherapeutic company, Agenus, a multi-type glioblastoma (GBMs) vaccine, Prophage G-200, combined with bevacizumab failed a phase II clinical trial that failed to exceed bevacizumab. The trial was also terminated early. . Argos and Agenus shares fell 66% and 16% respectively.
Drug source analysis
The development of tumor vaccines is progressing slowly. Last year, Aduro's Liszt bacteria platform was stopped by the FDA because of a patient infected with Listeria, and the GVAX/CRX-207 combination also failed in pancreatic cancer. Celldex's Rintega terminated early in a GBM Phase III clinical trial due to failure to improve overall survival. Rocapuldencel-T is an antigen presenting cell (APC) technology. This technique involves selecting from the patient's tumor sample some of the so-called new antigens, ie antigens that are unique to the tumor but not to normal cells. The mRNA of these antigens enters the patient's APC to express the new antigen in vitro, and then these brainwashed APCs are returned to the patient. The idea is that these APCs can activate T cells against the tumor's new antigen in vivo, thereby killing the tumor. Normal cells are not harmed. Earlier, an APC-like Provenge (sipuleucel-T, in vitro expanded APC) was approved for prostate cancer, and this product was recently introduced to China.
Prophage G-200 also utilizes patient-specific new tumor antigens, but binds to these antigens in vitro with heat shock proteins instead of APC, and then returns the heat shock protein/new antigen complex as an antigen to the patient. The main function of this type of scaffold protein is to bind to other proteins and is therefore an important immunological adjuvant. Prophage G-200 has shown good efficacy in small clinical trials, with GBM, a refractory tumor patient, achieving median survival for nearly three years. Rocapuldencel-T also showed amazing results in a small trial of 20 people, 5 of whom survived for more than 5 years. This also reminds everyone that small clinical trials are noisy, and even indications with small placebo effects such as tumors are not reliable.
Immunotherapy is the most popular direction for new tumor drugs. Cytokine IL2, preventive/therapeutic vaccine, checkpoint inhibitor, oncolytic virus and bispecific antibody have been listed. CAR-T is also expected to be launched this year. However, these therapies either target autoantigens expressed mainly in tumor cells, or activate the immune system indiscriminately, so the restriction is large. Now CAR-T has only a few blood tumors such as CD19 and BCMA, which have acceptable treatment windows. Even these CAR-Ts are risky and require hospitals with higher first aid capabilities. Although there are some clues to solid tumors, there are currently no reliable CAR-T or bispecific antibody targets.
Therefore, it is a good idea to activate immune cell therapy against new antigens. To become a tumor, a tumor must first have some genetic variation, so it will produce a protein different from normal cells. Now the most visible biotech company, Moderna, is doing this business, and Roche joined the BioNTech last year to enter the field. But the search for a technology that is sufficiently expressed in tumor cells to produce enough T cells to respond to new antigens is not yet mature, so this idea is attractive, but how much input is needed to convert into new therapies that are now unpredictable. Like other new technologies, bad things happen to good ideas. Subversive technologies such as antibody drugs, RNA drugs, and nano-delivery have experienced 20-30 years of hard development, so high-selectivity, highly accurate individualized immunotherapy may also require a long growth period.
Source: US and Chinese medicine source (micro signal meizhongyaoyuan)
Animal Medicine Premix,Tilmicosin Premix,Tylvalosin Tartrate Premix,Animal Products Medicine
Sichuan Aibang Weiye Biological Engineering Co., Ltd. , https://www.aibangpharm.com