6.7.3 Statistics for Clinical Trials of TCR-T-Cell...
Among the 376 clinical trials containing the keyword “TCR” published on ClinicalTrials.gov updated by June 11, 2018, 84 of these trials have been identified to employ TCR-T-cell therapy technique by manual curation.Certain patterns can be revealed from these 84 clinical trials.Since June 11, when the data were gathered, to July 28, 13 more trials were included in ClinicalTrials.gov,where only 1 was related to TCR-T-cell therapy and was targeting HPV E6 antigen [192,193].
First, the start years of these clinical trials have shown a peculiar pattern.Three earliest clinical trials for TCR-T-cell therapy began in 2004.Since then, starting in 2006, the number of clinical trials started each year has shown a periodic pattern of fluctuation for every 3 or 4 years.Take the 8 years from 2006 to 2013 as an example, from 2006 to 2008, the number of clinical trials showed a steady increase and reached a peak in 2008, but the number then experienced a decrease in 2009,followed by a steady increase from 2010 to 2012 and then a decrease in 2013, and so on, but demonstrating an overall trend of increase in number of clinical trials from 2004 to 2018.This may be due to the fact that funds are periodically injected in this field, and it may require a period of 3 or 4 years to reach another peak in the number of clinical trials, whereas the demand and interest for TCR-T-cell therapy have increased in the long run due to its huge potential.28 of these 84 clinical trials are expected to be completed in 2019 and 2020.It will be the best time to evaluate the results of the TCR-T application over other immunotherapy approaches [193].
Second, about 57% of these clinical trials (48 clinical trials) are still recruiting, whereas only less than one-quarter of these clinical trials (20 clinical trials) are either terminated or completed.This proves that TCR-T-cell therapy is still a relatively new target for research, compared to CAR-T-cell therapy, indicating that TCR-T-cell therapy may have huge potential in the future [193].(https://www.daowen.com)
Third, about 42% of these trials (35 trials) are for phase 1 clinical trials, whereas approximately 33% of these trials (28 trials) are for both phase 1 and phase 2 clinical trials, again showing that most of the TCR-T clinical trials are at the start of development, and the application of TCR-T-cell therapy in industries or hospitals is still a long way to go [193].
Fourth, more than half of the antigens targeted by the 84 clinical trials (43 trials) are CT antigens,and 31 of these 43 trials target NY-ESO-1 (30 trials target NY-ESO-1, 1 trial targets NY-ESO-1&LAGE-1A), probably because the NY-ESO-1-specific TCR-T cells have been most thoroughly examined and tested in terms of therapeutic potentials in synovial cell sarcoma,melanoma, and myeloma.Only 3 trials are targeting neoantigens, probably due to the fact that it requires a great deal of time and costs to perform the sequencing as well as to identify the effective TCRs for each patient and the same process needs to be repeated for each individual patient.On the other hand, if the method of sequencing and good manufacturing process can be made more efficient and cost-effective, such as applying robotics system to make sequencing faster and using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system or sleeping beauty transposons, neoantigens can be of huge potential without much competition for TCR-T industries [193].
Finally, the most frequently targeted cancer type is melanoma, being the target of 33 trials.This is probably because that the frequency of melanoma cases is high.Melanoma accounts for almost 92% of new cases of skin cancer and about 69% of skin cancer-related death in the United States in 2018, and the incidence of melanoma has been increasing at a faster rate than the majority of other cancers.Another reason might be that melanoma lesions are relatively accessible and that the nature of melanoma to easily adapt to tissue culture means that tissue samples and cell lines can be readily available for research purposes, making melanoma being preferred by clinical trials.Leukemia and gastrointestinal cancers fall as the second, being the target of 24 trials.Of the 210 cancers mentioned in 84 clinical trials, only 34 trials (approximately 16%) focuses on hematological malignancies only, so 84% of cancer types targeted by these 84 clinical trials belong to the category of solid tumor, possibly due to the fact that CAR-T has already well proved efficiency in treating hematological malignancies, whereas, as proven by multiple studies, its effects toward solid tumor has been proven unsuccessful as compared to TCR-T-cell therapy.Nevertheless, there have indeed been attempts to improve CAR-T cells’ performance against solid tumor because of such unsatisfactory results.Therefore, it is possible that CAR-T cells might be widely available for solid tumor treatment in the future [193].