Limits...
A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth.

Wen FT, Thisted RA, Rowley DA, Schreiber H - Oncoimmunology (2012)

Bottom Line: The predominant effect of cancer immunotherapies was slowed or delayed outgrowth.Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth.Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology; The University of Chicago; Chicago, IL USA.

ABSTRACT
We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords "immunotherapy" AND "cancer" for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5-121 mm(3) in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm(3) was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm(3), and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm(3), and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth.

No MeSH data available.


Related in: MedlinePlus

Figure 3. Most experimental immunotherapies published treat small tumors yet succeed only at slowing or delaying tumor growth, but in several recent reports, larger tumors are being treated and a few reports present tumor regression. An effect size (E) of 1 indicates the treatment arrested tumor growth. An E < 1 indicates that the treated tumor still grew progressively, but only slower than the control or in a delayed fashion, i.e., a reduction of the growth rate of the tumor. An E > 1 indicates tumor regression. (Left panel) Detailed analysis was done for all experimental cancer immunotherapy publications listed in PubMed for April, June, and November of 2010. Regression of tumors larger than 200 mm3 is observed only after passive antibody or adoptive T cell therapy. (n = 74). (Right panel) The same analysis was performed for those publications in the entire year of 1980. Very few publications presented analyzable data. No publication uses tumors larger than 200 mm3, and regression is not observed at all. (n = 10).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3377001&req=5

Figure 3: Figure 3. Most experimental immunotherapies published treat small tumors yet succeed only at slowing or delaying tumor growth, but in several recent reports, larger tumors are being treated and a few reports present tumor regression. An effect size (E) of 1 indicates the treatment arrested tumor growth. An E < 1 indicates that the treated tumor still grew progressively, but only slower than the control or in a delayed fashion, i.e., a reduction of the growth rate of the tumor. An E > 1 indicates tumor regression. (Left panel) Detailed analysis was done for all experimental cancer immunotherapy publications listed in PubMed for April, June, and November of 2010. Regression of tumors larger than 200 mm3 is observed only after passive antibody or adoptive T cell therapy. (n = 74). (Right panel) The same analysis was performed for those publications in the entire year of 1980. Very few publications presented analyzable data. No publication uses tumors larger than 200 mm3, and regression is not observed at all. (n = 10).

Mentions: Having characterized the distribution of tumor sizes employed in experimental immunotherapies, we asked what sort of therapeutic effect could be achieved on these tumors of varying sizes. The magnitude of the effect size (E) was expressed as a ratio of linearized growth rates of treated tumors against control tumors (Eqn. 1) (see Materials and Methods). The subset of publications from 2010 reporting therapeutically related experiments was used for detailed analyses. Equation 1 was applied to these experiments reported in 74 papers from April, June and November 2010, and the maximum effect size of multiple reported experiments for each respective paper was selected to represent that paper. In Figure 3, the effect size on tumor growth is plotted against tumor volume at the start of treatment. Despite the prevalence of experiments using small tumors, most succeed only at slowing or delaying tumor growth (0 < E ≤ 1). By contrast, of the four experiments using large tumors reported during these three months, two induce tumor regression (E > 1), and one arrests tumor growth (E = 1). Although the number of publications using large tumors is too few to draw definitive conclusions, we note that the therapies that induce regression of large tumors both use adoptive immune cell transfer. Other types of immunotherapy do not seem to follow a trend, and their effects are generally scattered.


A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth.

Wen FT, Thisted RA, Rowley DA, Schreiber H - Oncoimmunology (2012)

Figure 3. Most experimental immunotherapies published treat small tumors yet succeed only at slowing or delaying tumor growth, but in several recent reports, larger tumors are being treated and a few reports present tumor regression. An effect size (E) of 1 indicates the treatment arrested tumor growth. An E < 1 indicates that the treated tumor still grew progressively, but only slower than the control or in a delayed fashion, i.e., a reduction of the growth rate of the tumor. An E > 1 indicates tumor regression. (Left panel) Detailed analysis was done for all experimental cancer immunotherapy publications listed in PubMed for April, June, and November of 2010. Regression of tumors larger than 200 mm3 is observed only after passive antibody or adoptive T cell therapy. (n = 74). (Right panel) The same analysis was performed for those publications in the entire year of 1980. Very few publications presented analyzable data. No publication uses tumors larger than 200 mm3, and regression is not observed at all. (n = 10).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3377001&req=5

Figure 3: Figure 3. Most experimental immunotherapies published treat small tumors yet succeed only at slowing or delaying tumor growth, but in several recent reports, larger tumors are being treated and a few reports present tumor regression. An effect size (E) of 1 indicates the treatment arrested tumor growth. An E < 1 indicates that the treated tumor still grew progressively, but only slower than the control or in a delayed fashion, i.e., a reduction of the growth rate of the tumor. An E > 1 indicates tumor regression. (Left panel) Detailed analysis was done for all experimental cancer immunotherapy publications listed in PubMed for April, June, and November of 2010. Regression of tumors larger than 200 mm3 is observed only after passive antibody or adoptive T cell therapy. (n = 74). (Right panel) The same analysis was performed for those publications in the entire year of 1980. Very few publications presented analyzable data. No publication uses tumors larger than 200 mm3, and regression is not observed at all. (n = 10).
Mentions: Having characterized the distribution of tumor sizes employed in experimental immunotherapies, we asked what sort of therapeutic effect could be achieved on these tumors of varying sizes. The magnitude of the effect size (E) was expressed as a ratio of linearized growth rates of treated tumors against control tumors (Eqn. 1) (see Materials and Methods). The subset of publications from 2010 reporting therapeutically related experiments was used for detailed analyses. Equation 1 was applied to these experiments reported in 74 papers from April, June and November 2010, and the maximum effect size of multiple reported experiments for each respective paper was selected to represent that paper. In Figure 3, the effect size on tumor growth is plotted against tumor volume at the start of treatment. Despite the prevalence of experiments using small tumors, most succeed only at slowing or delaying tumor growth (0 < E ≤ 1). By contrast, of the four experiments using large tumors reported during these three months, two induce tumor regression (E > 1), and one arrests tumor growth (E = 1). Although the number of publications using large tumors is too few to draw definitive conclusions, we note that the therapies that induce regression of large tumors both use adoptive immune cell transfer. Other types of immunotherapy do not seem to follow a trend, and their effects are generally scattered.

Bottom Line: The predominant effect of cancer immunotherapies was slowed or delayed outgrowth.Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth.Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology; The University of Chicago; Chicago, IL USA.

ABSTRACT
We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords "immunotherapy" AND "cancer" for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5-121 mm(3) in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm(3) was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm(3), and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm(3), and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth.

No MeSH data available.


Related in: MedlinePlus