Nghiên cứu đánh dấu kháng thể đơn dòng kháng CD20 với đồng vị phóng xạ i 131 dùng trong điều trị bệnh ung thư máu

BO KHOA HOC VA CONG NGHE VIEN NANG Ll/ONG NGUYEN TlT VIET NAM VlfN NGHIEN ctru HAT NHAN BAO CAO TONG KET THlTC HIEN DE TAI cAP BO NAM 2007 - 2008 TEN DE TAI NGHIEN ClTU DANH DAU KHANG THE BON DONG KHANG CD20 V6l DONG VI PHONG XA 1-131 DUNG TRONG DIEU TRI BENH UNG THU* MAU Ma s6: 05/07-09/NLNT Chu nhifm de tai: ThS. Nguyen Thj Thu THANG 12/2009 DANH SACH NHlTNG NGircn THAM GIA THlTC HIEN DE TAI Nguyen Thi Thu ThS. NCV Duong Van Dong ThS. NCVC V6 Thi Cam Hoa CN, NCV Chu Van Khoa Mai Phudc Tho ThS, NCV Biii Van Cucmg CN, NCV CN, NCV Pham Ngoc Dien CN, NCV Mai Trong Khoa PGS. TS. Le Quang Huan PGS. TS. 10 Le Ngoc Ha TS. BS Trung Tam Nghien cuu va dieu che Dong vi Phong xa, Vien Nghien cuu Hat nhan Trung Tam Nghien cuu va dieu che Dong vi Phong xa, Vien Nghien ciru Hat nhan Trung Tam Nghien cuu va dieu che Dong vi Phong xa, Vien Nghien cuu Hat nhan Trung Tam Nghien ciiu va dieu che Dong vj Phong xa, Vien Nghien cim Hat nhan Trung Tam Nghien ctiu va dieu che Dong vj Phong xa, Vien Nghien cuu Hat nhan Trung Tam Nghien cuu va dieu che Dong vi Phong xa, Vien Nghien cuu Hat nhan Trung Tam Nghien cuu va dieu che Dong vi Phong xa, Vien Nghien ciiu Hat nhan Trung Tam Y hoc hat nhan va Dieu tri ung budu, Benh vien Bach Mai, Ha Noi Vien Cong Nghe Sinh hoc, Vien Khoa hoc Viet Nam Benh Vien 108, Ha Noi Cac ca quan, don vi phoi hap thye hien 1. Vien Cong nghe sinh hoc. Ha Noi 2. Benh vien Bach Mai, Ha Noi 3. BenhvienlOS, HaNoi ^^n MUC LUC • • Trang Trang bia Danh sach nhimg ngudi tham gia thuc hien de tai 1 Muc luc 2 Abstract 5 Tom tat 6 Md dau 7 I. Tom tat tinh hinh nghien cuu trong va ngoai nudc 8 II. Muc tieu cua de tai 9 III. Tom tat noi dung nghien ctju 10 Phan I: TONG QUAN I. Gioi thieu nhirng tien bo moi trong dieu tri mien djch phong xa RIT 11 1.1. Cac Idiai niem 11 1.2. Khang the dugc sir dung dieu tri nham dich 12 1.3. Cac tac nhan chup hinh mdi trong RIT 18 1.4. L/ng dung RIT trong dieu tri NHL 18 II. Cac thanh phan co* ban trong RIT 21 II. 1. Khang nguyen CD20 vai tro va tiem nang ung dung 21 11.2. Khang the va cong nghe tao khang the 23 11.3. Dong vi phdng xa 28 III. Cac phirong phap danh dau khang the voi dong vj phong xa 30 III. 1. Dac diem chung 30 111.2. Qua trinh danh dau phong xa 31 111.3. Phuang phap danh dau khang the vdi '^'l 32 111.4. Phuang phap danh dau khang the vdi '^'^'"Tc va ' "in 35 IV. Nghien cihi du-ffc dong hoc 37 Phan II: VAT LIEU VA PHT/ONG PHAP NGHIEN ClTU 38 I. Nguyen lieu, hoa chat, thiet bi II. Nghien ciru cac dieu kien toi ini danh dau khang the voi phong xa 39 II. 1. Xac djnh ham'lugng ChT ' 39 11.2. Xac dinh ham lugng khang the, hoat do, thdi gian phan ung 42 11.3. Xac dinh pH 43 11.4. Quy trinh danh dau khang the 44 11.5. Danh dau theo hoat do rieng 46 11.6. Phan ung mien dich 47 11.7. Phuong phap iodogen 48 U.S. Danh dau khang the don chuoi 49 III. Kiem tra chat Iirong san pham 49 III. 1. Kiem tra do sach hda phdng xa 49 111.2. Kiem tra do vd khuan 50 111.3. Kiem tra ngi doc td vi khuan 51 111.4. Kiem tra do dn dinh trong huyet thanh 53 111.5. Kiem tra do dn dinh theo thdi gian bao quan 53 111.6. Kiem tra phan bd sinh hoc tren chupt 53 III.7. Kiem tra dao thai thudc tren thd 53 IV. Chup hinh phan bo thuoc phase I tren benh nhan ung thir NHL 54 Phan III: KET QUA NGHIEN CUtl I. Ket qua danh dau khang the 56 1.1. Ket qua kiem tra chat lugng '^'l danh dau 56 1.2. Ket qua khao sat ham lugng ChT 58 1.3. Ket qua khao sat ham lugng, hoat dp, thdi gian 61 1.4. Kit qua khao sat pH 62 1.5. Ket qua dieu che san pham 63 1.6. Ket qua dieu che san pham theo hoat dp rieng 64 1.7. Ket qua kiem tra hoat tinh mien dich 65 1.8. Ket qua danh dau khang the bang phuong phap iodogen 66 1.9. Ket qua danh dau khang the dcm chudi 67 II. Ket qua kiem tra chat Iirong dirtfc chat phong xa 68 II. 1. Kiem tra dp sach hoa phdng xa 68 11.2. Ket qua kiem tra dp vd khuan 71 11.3. Ket qua kiem tra npi doc td vi khuan 72 11.4. Kiem tra dp dn dinh trong huyet thanh ngudi 73 11.5. Kiem tra dp dn dinh theo thdi gian 74 11.6. Kiem tra phan bd sinh hpc 76 11.7. Kiem tra dao thai sinh hpc 78 III. Ket qua chup hinh phan bo thuoc phase I tren benh nhan ung thir 80 Phan IV: KET LUAN 85 Tai lieu tham khao 86 Giai trinh cac khoan chi 87 Phu luc 1: Tdng hgp khang the don chuoi Phu luc 2: Kiem tra chat lugng Phu luc 3: Lam sang Phu luc 4: Thdng tin de tai BANG VIET TAT RIT Lieu phap mien dich phdng xa (radioimmunotherapy) RJS Chup hinh nhap nhay mien dich (Radioimmunoscintigraphy) CD Cum biet hoa (cluster differentiation) MAb Khang the don ddng (monoclonal antibody) NHL U lympho khdng Hogdkin (non-Hodgkin's lymphoma) FDA Cue quan ly thudc va thuc pham Hoa Ky (Food and Drug Administration) BCA Tac nhan chelat hda hai chuc nang (bifunctional chelating agent) CR Dap ling toan phan (complete response) PFS Tiep tuc sdng sdt (progression-free survival) PR Dap ung rieng phan (partial response) ADCC Doc tinh vdi te bao qua khang the (Antibody Dependent Cellular Cytotoxicity) CDC Ddc tinh vdi te bao qua bd the (Complement Dependent Cytotoxicity) CDCC Ddc tinh vdi te bao phu thudc bd the (Complement Dependent Cellular Cytotoxicity) CLL Benh mau trang dang te bao lympho man tinh (Chronic Lymphocytic Leukemia) AML Ung thu bach cau dang tuy (Acute Myeloid Leukemia) ALL Ung thu nguyen bao tuy cap (Acute Lymphoblastic Leukemia) RAIT Dieu tri phdng xa mien dich HACA Khang khang the lai d ngudi (Human Anti-Chimeric Antibody) HAMA Khang khang the chupt (Human Anti-Murine Antibody) HAHA Khang khang the nhan hoa d ngudi (Human Anti-humanized Antibody) IL-6 Interleukin 6 Rf Retardation factor (retention factor) NSB Phan gan khdng dac hieu (non specific binding) EGFR Epidermal Growth Factor Receptor HER 2 Herceptin, khang the chira ung thu vii HAT Hypoxanthin Aminopterin Thymidin VEGF Vascular Endothelial Growth Factor CDR Viing trinh dien khang nguyen FACS phan loai te bao phat huynh quang (Fluorescence activated cell sorting) IgG Immunoglobulin Sc-FvAb Khang the don chuoi (Single-Chain Fragment Variable Antibody) cfii Don vi do mat dp vi sinh (Colony forming unit) ChT Chloramin T ITLC Sac ky lop mdng ttic thdi (Instant Thin Layer Chromatography) FPLC Fast Protein Liquid Chromatography STUDY ON THE RADIOLABELING OF MONOCLONAL ANTIBODY FOR BLOOD CANCER THERAPY Nguyen Thi Thu Abstract In recent years, radioimmunotherapy (RIT) has become a highly promising oncologic therapeutic modality with established clinical efficacy, particularly in the therapy of haematological malignancies. Anti CD20 monoclonal antibody was labelled with '^'l used in the treatment of B cell non Hodgkin's Lymphoma (NHL), B cell leukemia. In this study, the monoclonal antibody Rituximab was labelled with '^'l using chloramin T method (ChT). The optimized ChT concentration for the oxidation of 185 MBq of Na'^'l solution and 750|ag of Rituximab was 50\igl50n\. The reaction time was 5 minutes at room temperature. The labeling reaction has stopped using natrimetabisulphite (SMB). Labelling efficacy was controlled by ITLC. The reaction mixture was purified through the Sephadex G-25 PDIO Pharmacia column. The collected '^'l-CD20MAb Rituximab was filtered through a 0.20^m milipore sterile filter. The radiochemical labeling yield was more than 95%. Radiochemical purity of the radiopharmaceutical after purification was more than 99%. The product has passed the test for sterility, bacterial endotoxins, to be sufficiency invivo and invitro stable after labeling, ready for clinical use. In the phase I trial, a radiation absorbed dose escalation and protein mass dose escalation were undertaken. '^'l-CD20MAb be used on two patients with blood cancer type NHL, has recorded immunoscintigraphy biodistribution. The radiolabeled antibody used in clinical is safe and efficacy. It's the radiopharmaceutical used in cancer therapy with RIT. This study has the goal of research and develop and clinical testing. It has the potential to be a new method of treatment for RIT domestically. NGHIEN ClTU DANH DAU KHANG THE DON DONG V6l DONG VI PHONG XA DUNG TRONG DIEU TRI BENH UNG THU* MAU Nguyen Thi Thu Tom tat Trong nhirng nam gan day lieu phap mien dich phdng xa (RIT) da trd thanh phucmg thiic dieu tri ung thu day hiia hen vdi hieu qua lam sang ro ret dac biet la trong dieu tri cac ung thu mau. Khang the don ddng khang CD20 dugc danh dau vdi ddng vi phdng xa '^'l dimg trong dieu tri benh u lympho khdng Hodgkin (NHL), benh ung thu te bao B. Trong nghien ciiu nay, khang the don ddng Rituximab dugc danh dau vdi '^'l bang phuong phap Chloramin T. Ham lugng ChT tdi uu de oxy hoa 185MBq '^'l va 750ng Rituximab la 50p.g/50|il. Thdi gian phan iing la 3 phiit d nhiet dp phdng. Phan ung dugc dimg bang each them chat khu natri metabisulphite (SMB). Hieu suat danh dau dugc kiem tra bang phuong phap sac ky lop mdng ITLC. Hdn hgp phan iing dugc Ipc qua cdt Sephadex G25 PDIO. San pham '^'l-CD20MAb Rituximab dugc Ipc qua phii Ipc vd triing 0,20fxm. Hieu suat danh dau phdng xa hon 95%. Dp sach hda phdng xa cua san pham sau khi Ipc qua cot la hem 99%. San pham dat tieu chuan vd trung, dat tieu chuan kiem tra npi ddc td vi khuan, dn dinh invitro va invivo cd the sir dung cho lam sang. Trong phase I thir nghiem, lieu hap thu biic xa va lieu lugng protein dugc thuc hien. '^'l-CD20MAb Rituximab dugc sir dung lam sang tren hai benh nhan ung thu mau dang NHL, da ghi hinh nhap nhay mien dich phan bd thudc. Khang the danh dau phdng xa cd the sir dung tren lam sang an toan va hieu qua. Day la dugc chat phdng xa diing trong dieu tri ung thu bang ky thuat mien dich phdng xa RIT. De tai da dat ra muc tieu nghien ctiu dieu che va thir nghiem va cd tiem nang md dau cho hudng dieu tri mien dich phdng xa trong nudc. MOfDAu Trong thap nien qua, ciing vdi su ra ddi va ngay cang hien dai hda cac thiet bi chup hinh chan doan nhu may chup cat Idp dien toan SPECT va may chup cat Idp diing ddng vi phdng xa phat positron PET-CT, nhieu the he thudc phdng xa mdi cQng da dugc nghien ciiu dieu che va phat trien. Su phat trien ddng bp nay da lam ddi mdi bp mat cua y hpc hat nhan bdi chat lugng chan doan va hieu qua dieu tri. Ben canh nhiing chan doan chinh xac de phat hien benh, viec nghien ciiu chiia tri benh la nhiem vu hang dau cua y hpc. Mot trong nhiing noi bat cua y hpc hat nhan trong tri lieu la viec sir dung khang the don ddng danh dau vdi ddng vi phdng xa dung trong dieu tri ung thu. Ky thuat dieu tri benh bang phdng xa da ra ddi tir nhiing nam 1950 tir khi y hpc biet dung '•"l trong dieu tri tuyen giap. Tir do den nay, cac dugc chat phdng xa danh dau vdi ddng vi ' 'l khdng ngimg nghien ciiu va phat trien. Dac biet la trong nhirng nam gan day, khang the don ddng danh dau phdng xa da dugc diing trong chan doan va dieu tri lam sang. Phuong phap chiia benh dung khang the don ddng gpi la phuong phap dieu tri nham dich. Phuong phap dieu tri nay cdn dugc gpi la lieu phap phdng xa mien dich RIT (Radioimmunotherapy). Nhd nhimg tien bd cua cdng nghe sinh hpc va nhiing hieu biet ve sinh hpc phan tir va sinh hpc te bao, RIT da trd thanh lieu phap chiia tri ung thu day hiia hen vdi nhirng hieu qua lam sang ro ret. U lympho khdng Hodgkin (NHL) la benh ung thu cac lympho bao B trong mau, khi bi ung thu, tren be mat cac lympho bao B nay bieu hien khang nguyen la, bang ky thuat sinh hpc phan tir hien dai, cac nha khoa hpc tren the gidi da xac dinh dd la khang nguyen CD20 va cau tnic phan tii ciing da xac dinh. Phan tir khang the don ddng khang CD20 (Rituximab) dugc su dung lam sang tir nam 1997, phan tti khang the thuc hien chiic nang nham dich cua minh bang each gan dac hieu len khang nguyen dich, diet te bao ung thu bang cac co che biic xa ion hda (khi gan vdi chat phdng xa), co che gay ddc tinh vdi te bao ung thu qua khang the va gay ddc tinh vdi te bao ung thu qua bd the. Vdi thdi gian ban ra 8 ngay va phat tia gamma vdi nang lugng la 364 keV, va tia beta vdi nang lugng trung binh la 192 keV, '^'l la ddng vi phdng xa ly tudng cho viec chup hinh va dieu tri benh khi gan vdi phan tir khang the. Khang the khang CD20 da dugc gan vdi ddng vi phdng xa '^'l bang phuong phap danh dau phdng xa sir dung chloramin T lam chat oxy hda. Khang the danh dau dugc tinh che va kiem tra chat lugng theo tieu chuan cua thudc phdng xa de su dung lam sang. Day la dugc chdt phdng xa dimg trong dieu tri ung thu bang ky thuat RIT. D6 tai da dat ra muc tieu nghien ciiu dieu che, thu nghiem va md dau cho hudng dieu tri mien dich phdng xa trong nudc. I. Tinh hinh nghien ciru trong va ngoai niro^c: Ky thuat san xuat khang the don ddng da dugc hai nha bac hgc Cesar Milstein va Georges Kohler de ra vao nam 1975 da dugc giai thudng Nobel vao nam 1984 bdi nhieu iing dung cd gia tri vugt bac trong y hpc. Hien nay, tren the gidi vdi hon 200 Cdng ty nghien ciiu va san xuat khang the, da cd 23 khang the don ddng dugc FDA phe duyet cho sir dung lam sang, hang nghin loai dang trong qua trinh nghien ciiru lam sang. Nhieu loai khang the don ddng mdi da dugc nghien ciiru va cai tien, ddi mdi phuc vu cho cac muc dich chan doan va dieu tri trong y hpc. Nhiing ndi bat gan day nhat la sau hon 1/4 the ky ke tir khi ra ddi, viec sii dung khang the dcm ddng cho dieu tri ung thu mdi bat dau sir dung hieu qua tren lam sang. Bdi vi, trudc kia ngudi ta san xuat khang the don ddng theo phuong phap tao ra cac khang the tren chupt, do vay khi dua vao CO the con ngudi, he thdng mien dich se phat hien ra dd la chat ngoai lai, va se bi dap ling mien dich chdng lai va dao thai khdi vat chu. Do vay ma viec dieu tri van cdn gap nhieu han che. Trong nhirng nam 1986-1990, cac nha khoa hpc Michael Neuberger va Greg Winter da tao ra mot biit pha khi dua ra ky thuat cd ten gpi la "humanise". Nhd ky thuat nay, ddng khang the san xuat tir chupt dugc chuyen thanh ddng khang the ngudi, thich hgp cho viec sii dung tren co the con ngudi va md ra trien vgng mdi trong dieu tri ung thu. Trong vai nam gan day viec san xuat va sir dung khang the don ddng trong dieu tri ung thu la van de thdi sir tren toan the gidi. Dac biet la, mdt sd ddng vj phdng xa nhu ^^""Tc, '**Re, '"Sm, '"in, ^"Y, '^'I cd thl gan vdi khang the don ddng, dan dudng mot each dac hieu den cac te bao ung thu, cac chat phdng xa phat tia gamma ('y), giiip cho viec phat hien chan doan va theo doi ung thu, cac chat phdng xa phat tia beta (P) cd the tieu diet te bao ung thu. Sir phat trien nay ket hgp vdi su phat trien cdng nghe may tinh, cdng nghe thong tin lam cho nganh y hpc hat nhan ngay cang dat den dinh cao cua nen y hpc hien dai. Khang the don ddng khang CD20 da dugc dua vao su dung lam sang de chua benh ung thu tk bao lympho B. Day la khang the gan dac hieu len khang nguyen CD20, khang nguyen nay bieu hien vdi mat dp cao te bao lympho B ung thu. Tren the gidi, ngudi ta da dua khang the khang CD20 vao sir dung dieu tri lam sang tii nam 1997 vdi ten thucmg mai Rituximab. Viec tao conjugate vdi ddng vi phdng xa chi nghien ciiu trong vai nam gan day va chinh thiic dugc phep sir dung lam sang tir nam 2003, dd la cac san phdm Bexxar, Tositumomab. Trung tam Nghien cim va Di6u ch6 Ddng vi Phdng xa thudc Vien Nghien ciiu hat nhan, Vien Nang lugng nguyen tir Viet Nam la don vi duy nh4t trong nudc hien nay dang san xuat cac loai ddng vi phdng xa va dugc chdt phdng xa phuc vu cho viec chin doan va dieu tri benh. Mot sd ddng vi phdng xa chi san xuit dugc tren Id phan ring hat nhan va cd gia tri sir dung cao trong y hpc nhu ' 'l, ^^""Tc, •'^P, '"Sm Hien nay cac ddng vj phdng xa nay dugc san xudt va cung cdp thudng xuyen den cac co sd y hpc hat nhan trong nudc. Ciing vdi trang thik bi phuc vu cho viec san xudt va kilm tra chdt lugng cac dugc chdt phdng xa theo tieu chuan QA/QC/GMP cua qudc te, Trung tam ciing dugc ddu tu mdt sd trang thilt bi cho san xudt cac kit dinh lugng phdng xa mien dich (RIA), san xudt chdt danh ddu cac hocmon vdi ddng vi phdng xa, danh dau cac khang the vdi dong vi phdng xa, thuc hien cac nghien ciiu tdi uu qua trinh danh dau va dinh lugng. •' Cac nghien ciiru san xuat khang the don ddng danh ddu vdi ddng vi phdng xa hoac cac chdt khang ung thu cho muc dich chan doan va dieu tri ung thu ciing da dugc dat ra tir nhieu nam nay, nhung chua cd dieu kien de thuc hien. Trong cac benh ung thu mau, theo thdng ke, ung thu mau khdng Hodgkin la dang phd bien va xay ra ca d liia tudi thanh thieu nien. Viec nghien ciiu va san xuat cac dugc chat phdng xa khang the don ddng tai Viet Nam, phuc vu cho chan doan va dieu tri trong nudc la viec lam cd y nghia ldn cho xa hdi, cho cac benh nhan ung thu. Hien nay, trong nudc cac phdng thi nghiem tai cac trudng dai hpc Y, tai Vien Cdng Nghe Sinh Hpc Viet Nam dang thuc hien cac nghien ciiu ve san xuat khang the don ddng cho chan doan va dieu tri benh ung thu. Vi vay ITnh vuc nghien ciiu danh dau khang the don ddng trong nudc se cd dieu kien nghien ciiu va iing dung cho y hpc. II. Muc tieu nghien cihi Muc tieu cua de tai la hoan thanh quy trinh dieu che va kiem tra chat lugng dugc chat ca khang the dcm ddng khang CD20 danh dau vdi ddng vi phdng xa '^'l: Hoan thanh quy trinh danh dau khang the don ddng khang CD-20 vdi ddng vi phdng xa '^'I. - Hoan thanh cac quy trinh kiem tra chat lugng nhu kiem tra hieu suat danh dau, dp sach hda phdng xa, kiem tra dp dn dinh thudc, dp vd khuan, chi nhiet td, ndi ddc td vi khuan, cac kiem tra chat lugng sinh hpc nhu su phan bd thudc, su dao thai. - U'ng dung lam sang chup hinh phan bd thudc tren benh nhan ung thu mau khdng Hodgkin (NHL) phase I III. NQI dung nghien cihi: Thuc hien 4 ngi dung chinh sau 1) Tinh che khang the don dong Khang the don ddng don ddng khang CD20 dugc mua d dang tinh khiet, san sang dimg trong y hpc, dugc phan tich kiem tra bang sac ky Idng cao ap FPLC. 2) Danh dau khang the doti dong vdi dong vj phong xa ''''l Day la cdng doan quan trgng nhat de tao ra san pham chinh trong de tai, gdm cac budc sau: - Chpn phuong phap chloramin T (ChT): Diing chloramin T lam chdt oxy hda va natri metabisulphit (SMB) lam chat khu. - Khao sat hieu suat danh dau va cac yeu td anh hudng den hieu sudt danh ddu: Khao sat cac dieu ki?n tdi uu de dat hieu suat danh ddu hon 90%. - Khao sat ham lugng Chloramin T can thilt trong qua trinh danh ddu vdi phdng xa. - Khao sat thdi gian phan iing tdi uu dk gdn khang th6 vdi phdng xa. - Ty le khang the va hoat dp phdng xa '^'l. - Tach hon hgp phan iing qua cdt Ipc gel Sephadex G-25: Hgp chdt danh ddu se cd nhiSu thanh phdn, do vay hon hgp dugc tach phan doan tinh khilt khang th8 gdn vdi ddng vi [...]... ngu bdi 3 hinh thiic la giai phiu, biic xa va hoa tri Neu ung thu dugc phat hien sdm khi nd dugc dinh vi, giai phau hoac hire xa, cd the dii de kiem soat va loai trir triet de benh Dieu tri biic xa diln hinh gom chilu xa ngoai len viing dac biet ciia co the cd khdi u, hoac "hat gidng" biic xa se phat tia trong viing ap sat ung thu (brachytherapy) dang tiec la ung thu thudng dugc phat hien sau khi nd... RIT: Cac co che co ban trong RIT la sir phat lieu hire xa vao trong te bao ung thu (hinh 1.12) Te bao ung thu chju lieu biic xa ldn hon te bao binh thudng do sir gidi han ve khoang chay cua cac tia biic xa Te bao ung thu tiep xiic vdi biic xa trong khoang thdi gian lau [20] H -131 \ 'i' ^ 131 Hinh 1.12 Co che tieu diet ung thu bang biic xa Cac ddng vi phdng xa diing trong dieu trj RIT dugc tdm tat trong. .. thuat di truyen, dung hgp vimg bien ddi chudi nang va nhe ciia chupt vdi vimg hang djnh IgGl/K cua ngudi (hinh 1.9) Khang the lai tao thanh cd kha nang tieu diet cac te bao B in vitro va lam giam lugng te bao B trong mau ngoai vi in vivo Su giam te bao B trong tiiy xuong, lach va cac hach lympho chua dugc nghien cim ky [23] Vi = Vung bien doi chuoi nhe I I = Vung bien 3Si cua chuot •• Vung hixig dinh... Hodgkin 10 Phan I TONG QUAN TAI LIEU I Gidi thieu nhung tien bo moi trong dieu trj mien dich phong xa RIT Da qua hon hai thap ky, kl tir khi bao cao dau tien cua khang the dugc sir dung danh ddu vdi ^""Tc dk chup hirih vi tri di can ung thu true trang, viec chan doan va chira benh bang khang thl khdng ngimg phat triln va ddi mdi Lieu phap dieu tri mien dich phdng xa RIT (radioimmunotherapy) da tiln... 33,2/100.000 (nir) Ghi nhan nhirng benh ung thu hay gap d tre em tai 5 tinh thanh giai doan 2001-2004, NHL diing hang thiir hai d Ha Ndi (15%), Hai Phdng (15,4%), Thai Nguyen (14,3%), Thira Thien Hue (16,4%), diing thii ba d Cin Tho (20,9%) Tudi trung binh la 9, dinh cao nhit 7-10 tudi, dinh tilp theo la cudi tudi thieu nien Ti le nam:nii la 3:1 [51] 22 U lympho loai nay cd thl chuyin tdi miic do nang... Cac mien cdn lai cd trinh tu gidng nhau gpi la viing bat bien (C) So sanh trinh tu viing V cho thay tinh kha bien khdng phan bd deu ma tap trung vao ba viing gpi la cac viing sieu bien [2] Mofv . hgp cho viec sii dung tren co the con ngudi va md ra trien vgng mdi trong dieu tri ung thu. Trong vai nam gan day viec san xuat va sir dung khang the don ddng trong dieu tri ung thu la van de. hang dau cua y hpc. Mot trong nhiing noi bat cua y hpc hat nhan trong tri lieu la viec sir dung khang the don ddng danh dau vdi ddng vi phdng xa dung trong dieu tri ung thu. Ky thuat dieu. sir dung dieu tri nham dich 12 1.3. Cac tac nhan chup hinh mdi trong RIT 18 1.4. L/ng dung RIT trong dieu tri NHL 18 II. Cac thanh phan co* ban trong RIT 21 II. 1. Khang nguyen CD20