1、White PaperSelf-Driving CAR:The Promise of In Vivo CAR-T Therapy for Hematologic Malignancies EDWIN GUMAFELIX,Medical Director,APAC Cell and Gene Therapy Center of Excellence,IQVIALARA KRISTINA DONATO,Medical Director,APAC Medical Science and Strategy,IQVIAMARIA ROSELLE LUCAS,Senior Medical Director

2、,APAC Medical Science and Strategy,IQVIAMANFRED SEOW,Director,APAC Cell and Gene Therapy Center of Excellence,IQVIACLAUDIA CHONG,APAC Marketing Associate,R&D Solutions,IQVIACAMERON TURTLE,CLEARbridge Chair in Cancer Immunotherapy,University of SydneyTable of contentsIntroduction 1Global burden of he

3、matologic malignanciesTransformative impact of ex vivo autologous CAR-T therapiesCAR-T landscape in APAC countriesLimitations of conventional ex vivo CAR-T approaches Introduction to in vivo CAR-T therapy 6In vivo CAR-T paradigm 8Clinical advances and trialsChallenges and considerations 12Safety con

4、cerns and deliveryRegulatory considerationsFuture directions 13Conclusion 14What next?14References 15About the authors 20Acknowledgment 21 |1Global burden of hematologic malignanciesHematologic malignancies(HMs)represent a significant portion of the global cancer burden.This white paper focuses on i

5、n vivo-engineered T-cell therapy for three major HM subtypes of the B lineage:acute lymphoblastic leukemia(ALL),non-Hodgkin lymphoma(NHL),and multiple myeloma(MM).Over recent decades,the global incidence of HMs has steadily increased,while age-adjusted mortality rates have declined,largely due to ad

6、vances in treatment.1,2 In 2019,an estimated 1.34 million new cases of HMs were diagnosed worldwide1.Among these,leukemia had the highest global incidence,with around 643,580 cases reported.ALL accounts for a fraction of leukemia cases(153,320 new cases in 2019)and is more common in children than in