Correction to: Scientific Reports https://doi.org/10.1038/s41598-021-85329-9, published online 11 March 2021


The original version of this Article contained errors in the discussion of Atezolizumab aggregation, and anti-drug antibody development.


In the Abstract section,


"However, aglycosylated Atezolizumab is very unstable and easy to form aggregation, which causes quick development of anti-drug antibody (ADA) in 41% of Atezolizumab-treated cancer patients, eventually leading to loss of efficacy"


now reads:


"However, aglycosylated Atezolizumab is unstable and easy to form aggregates."


In the Introduction section,


“One of reasons contributing to the under-performance of Atezolizumab may be its high ADA rates in cancer patients. Quite a few Phase III clinical tries of Atezolizumab did not reach the clinical end point (in 2017, IMvigor211 for advanced bladder cancer failed in clinical Phase III; in 2018, IMblaze370 for colorectal cancer failed in clinical Phase III; in 2019, IMspire170 for melanoma failed in clinical Phase III)1.”


now reads:


“Quite a few Phase III clinical tries of Atezolizumab did not reach the clinical end point (in 2017, IMvigor211 for advanced bladder cancer failed in clinical Phase III; in 2018, IMblaze370 for colorectal cancer failed in clinical Phase III; in 2019, IMspire170 for melanoma failed in clinical Phase III)1.”


In addition, the text,


“It is well-known in antibody manufacturing that incomplete glycosylation will lead to aggregations of antibodies2, which in turn will induce strong ADA in treated patients3.”


now reads:


“It is well-known in antibody manufacturing that incomplete glycosylation will lead to aggregations of antibodies2, which in turn may induce ADA3.”


And the text,


“In its pre-clinical study, 100% of Atezolizumab-treated monkeys developed strong ADA. In clinical studies, even though their immune systems had been severely damaged by chemo or radiotherapy, 41.5% of the cancer patients developed ADA4. The fast development of neutralizing ADA forced the dosage of Atezolizumab to be escalated to a record high of 1200 mg per injection,4 and still failed to reach end-points in several Phase III clinic trials1.”


now reads:


“In its pre-clinical study, 100% of Atezolizumab-treated monkeys developed strong ADA. In clinical studies, even though their immune systems had been severely damaged by chemo or radiotherapy, 41.5% of the cancer patients developed ADA4. However, it should be noted that ADA was observed to have no clinically significant effect on the incidence or severity of adverse reactions4.”


In the Results section:


"High molecular weight (HMW) aggregates in antibody drugs are the major causes of anti-drug antibody (ADA)3"


now reads:


"High molecular weight (HMW) aggregates in antibody drugs can induce anti-drug antibody (ADA)3, though this has not been directly observed for Atezolizumab."


In addition, the text,


“Moreover, as shown in Table S4 and Fig. 4B, the Tagg of Maxatezo is 71.2 °C, which is 10.5 °C higher than that of Atezolizumab (60.7 °C), indicating that Maxatezo produced much less aggregates than Atezolizumab.”


now reads:


“Moreover, as shown in Table S4 and Fig. 4B, the Tagg of Maxatezo is 71.2 °C, which is 10.5 °C higher than that of Atezolizumab (60.7 °C), suggesting that Maxatezo will produce less aggregates than Atezolizumab.”


And the text,


“As shown in Fig. 5, Atezolizumab induced extremely high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). The ADA titers of Maxatezo in mice was significantly less than that of the aglycosylated Atezolizumab. Since both Atezolizumab and Maxatezo have almost identical humanized mouse antibody sequences except the insertion of GGGS and mutation N297A, we believe that the great differences of immunogenicity we observed in mice is due to the difference of aggregation levels in the antibody drugs, and we expect to see a significant reduction of ADA in Maxatezo-treated human patients.”


now reads:


“As shown in Fig. 5, Atezolizumab induced high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). The ADA titers of Maxatezo in mice was significantly less than that of the aglycosylated Atezolizumab. Since both Atezolizumab and Maxatezo have almost identical humanized mouse antibody sequences except the insertion of GGGS and mutation N297A, we think that the differences of immunogenicity we observed in mice is due to the difference of aggregation levels in the antibody drugs.”


The original Article has been corrected.