Isolation and characterization of spontaneously immortalized B‐lymphocyte lines from HIV‐infected patients with and without non‐Hodgkin's Lymphoma

Background: Non-Hodgkin’s lymphoma (NHL) is a primary malignancy in the lymphatic system and extranodal lymphoid tissue originating from B lymphocyte cells, T lymphocytes or natural killer (NK) cells. The incidence of NHL continues to increase with various characteristics. Objective: To find out the characteristics of NHL sufferers undergoing treatment in Otorhinolaryngology Head and Neck Surgery Department of dr. Zainoel Abidin Regional General Hospital (RSUDZA), Banda Aceh from January 2015 to December 2018. Method: This was an observational descriptive study conducted at Banda Aceh RSUDZA using retrospective secondary data collection from medical records that met the inclusion criteria, in total sampling method. Result: Found 32 research subjects, dominantly male (20), the highest age range was 56-65 years (10). The main complaints were neck lumps (10) and oropharynx lumps (11). The most common NHL was from B lymphocyte cells (6). The chemotherapy regimens used are cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The most frequent side effects are anemia, hypoalbuminemia, and leukopenia. Conclusion: The results showed that NHL was most common in men with an increased incidence in the fifth decade. Neck lumps are the most common complaint. The chemotherapy regimen used is CHOP and R-CHOP.Keywords : Non-Hodgkin’s Lymphoma, chemotherapy ABSTRAK Latar belakang: Limfoma Non-Hodgkin (LNH) adalah keganasan primer pada sistem limfatik dan jaringan limfoid ekstranodal yang berasal dari sel limfosit B, limfosit T atau sel natural killer (NK). Kejadian LNH terus meningkat dengan berbagai karakteristik. Tujuan: Melihat karakteristik penderita LNH yang menjalani pengobatan di Departemen THT-KL RSUD dr. Zainoel Abidin (RSUDZA), Banda Aceh pada periode Januari 2015 sampai Desember 2018. Metode: Penelitian deskriptif observasional dengan pengambilan data sekunder secara retrospektif dari rekam medis yang memenuhi kriteria inklusi, dengan metode total sampling. Hasil: Didapatkan total subjek penelitian 32 orang, dominan pada lakilaki (20), rentang usia tertinggi antara 56-65 tahun (10). Keluhan utama terbanyak adalah benjolan di leher (10) dan benjolan orofaring (11). LNH yang berasal dari sel limfosit B paling banyak dijumpai (6). Regimen kemoterapi yang digunakan adalah cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) dan rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Efek samping paling sering adalah anemia, hipoalbuminemia dan leukopenia. Kesimpulan: Hasil penelitian menunjukkan LNH paling sering pada laki-laki dengan angka kejadian meningkat pada dekade kelima. Keluhan yang paling sering adalah benjolan di leher. Regimen kemoterapi yang digunakan adalah CHOP dan R-CHOP.

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Radiobiological characterization of two human chemotherapy-resistant intermediate grade non-Hodgkin's lymphoma cell lines

Radiation Oncology Investigations ◽

10.1002/(sici)1520-6823(1999)7:3<158::aid-roi4>3.0.co;2-b ◽

1999 ◽

Vol 7 (3) ◽

pp. 158-162 ◽

Cited By ~ 1

Author(s):

Amr Aref ◽

Razmi Mohammad ◽

Mark Yudelev ◽

Rajani Choudhuri ◽

Amy Strowbridge ◽

...

Keyword(s):

Cell Lines ◽

Hodgkin’S Lymphoma ◽

Lymphoma Cell ◽

Hodgkin's Lymphoma ◽

Intermediate Grade ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

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Construction and Characterization of a Novel Ribonuclease Immunotoxin Consisting of Two Ranpirnase (Rap) Molecules Fused to an Internalizing Anti-CD74 Humanized IgG4 Antibody.

Blood ◽

10.1182/blood.v104.11.3289.3289 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3289-3289

Author(s):

Sailaja S. Vanama ◽

Puja Sapra ◽

Hans J. Hansen ◽

Ivan D. Horak ◽

David M. Goldenberg ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

Xenograft Model ◽

Hodgkin's Lymphoma ◽

Light Chains ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Sds Page

Abstract Ranpirnase (Rap), isolated from frog (Rana pipiens) oocytes, is a monomeric ribonuclease (MW 11800) that kills cells by degrading t-RNA upon internalization. Previous studies indicated that the cytotoxicity of Rap could be enhanced more than 10,000-fold when the enzyme is chemically conjugated to an internalizing antibody. Here we describe the construction and characterization of 2L-Rap-hLL1-γ4P, composed of two Rap molecules fused to hLL1, an internalizing anti-CD74 humanized monoclonal antibody. To reduce unwanted cytotoxicity, the IgG1 constant region of hLL1 was replaced with an IgG4 that contains a proline mutation in the hinge region. The Rap gene was inserted at the N-terminus of the light chain in the expression vector of hLL1 and expressed in NS0 mouse myeloma cells. The fusion protein was characterized by a variety of techniques, including SE-HPLC, SDS-PAGE, in vitro transcription translation (IVTT) assay using luciferase reporter system, and competition ELISA to measure the binding affinity for CD74. The in vitro potency was determined in non-Hodgkin’s lymphoma (Daudi) and multiple myeloma (MC/CAR) cell lines by MTS tetrazolium dye reduction assay. In vivo pharmacokinetics and biodistribution of radiolabeled 2L-Rap-hLL1- γ4P was compared to radiolabeled hLL1 mAb in naïve mice and in vivo therapeutic efficacy of 2L-Rap-hLL1- γ4P was determined in a xenograft model of Burkitt’s non-Hodgkin’s lymphoma (Daudi). Purified 2L-Rap-hLL1- γ4P was shown to be a single peak by SE-HPLC and its MW determined by MALDI-TOF to be 177,150, which is in agreement with the MW of one IgG (150,000) plus two Rap molecules (24,000). Reducing-SDS-PAGE of 2L-Rap-hLL1- γ4P revealed the presence of 3 bands, one corresponding to the heavy chain and the other two appearing to be derived from the Rap-fused light chains (38,526 and 36,700 by MS). Occurrence of the 2 light chains was shown to be due to glycosylation of Rap at the N69 residue. The binding affinity of 2L-Rap-hLL1- γ4P for CD74 was indistinguishable from that of hLL1. Both 2L-Rap-hLL1- γ4P and hLL1 bound to CD74 with subnanomolar affinity. The EC50 of RNase activity, as measured by the IVTT assay, was 300 pM for 2L-Rap-hLL1- γ4P and 30 pM for recombinant Rap (expressed in E. coil). In in vitro cytotoxicity assays, 2L-Rap-hLL1- γ4P was significantly cytotoxic against Daudi (EC50 280 pM) and the myeloma cell line, MC/CAR (EC50 50 nM). In contrast, free Rap or naked hLL1 did not demonstrate significant cytotoxicity at the concentrations tested. In vivo, the pharmacokinetic profile of 2L-Rap-hLL1- γ4P was almost identical to that of naked hLL1. Both 2L-Rap-hLL1- γ4P and hLL1 showed biphasic clearance from the circulation; the α and β half-life (t1/2) of 2L-Rap-hLL1- γ4P were 5 h and 119 h, respectively, and those of hLL1 were 4 h and 125 h, respectively. In tissue biodistribution studies, no significant difference was observed between 2L-Rap-hLL1- γ4P and hLL1 with regards to normal tissue uptake. Early efficacy results in the Daudi Burkitt’s non-Hodgkin’s lymphoma xenograft model demonstrate that treatment with a single dose of 2L-Rap-hLL1- γ4P as low as 1 μg/mouse significantly improves survival in comparison to untreated control mice (P<0.0001).

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Tumor Targeting, Dosimetry and Clinical Response Data for Lymphorad-131 (LR131; Iodine I-131 Labeled B-Lymphocyte Stimulator) in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.750.750 ◽

2004 ◽

Vol 104 (11) ◽

pp. 750-750 ◽

Cited By ~ 6

Author(s):

Andrew Belch ◽

Alexander McEwan* ◽

Joanne Hewitt* ◽

Terence Riauka ◽

Michael Stabin* ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Pet Imaging ◽

Hodgkin’S Lymphoma ◽

B Lymphocyte ◽

Hodgkin's Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

B Lymphocyte Stimulator

Abstract LR131 is a novel radioconjugate consisting of B Lymphocyte Stimulator (BLyS) protein, a B cell maturation factor of the TNF family that binds selectively to immunoglobulin-positive B cells, labeled with Iodine I 131. BLyS receptors are present on normal B cells and B cell malignancies. Ten subjects with relapsed, refractory follicular non-Hodgkin’s lymphoma (8M/2F, age 33–61) have been entered on study at the Cross Cancer Institute as part of a multicenter phase 1 dose escalation trial. FDG-PET and CT imaging were performed prior to and following LR131 therapy to evaluate tumor response and recurrence. Previous therapies for these patients included single and multiagent chemotherapy, limited field external beam radiation therapy and Rituximab with/without concomitant chemotherapy. Patients had an average of 2.6 previous therapies (range 1–4). Patients received an imaging/dosimetry dose of 5–7 mCi of LR131 followed 1–2 weeks later by the therapeutic dose. CT and PET confirmed specific tumor localization in all patients. Ten of ten patients targeted sites of disease seen on CT and PET with LR131 although one patient with rapidly progressing end stage disease did not uniformly target a very large tumor mass in the abdomen/pelvis. Administered activities for therapy were 0.35 mCi/kg (10 m g/kg BLyS), 0.70 mCi/kg (30 m g/kg BLyS), 1.35 mCi/kg (75 m g/kg BLyS) and 1.70 mCi/kg (75 m g/kg BLyS) for the first four cohorts, respectively. Of 8 evaluable patients through at least 12 weeks of follow-up there were 2 CRu, 2 PR and 1 SD. In the two patients with CRu, follow-up PET scanning was negative for FDG accumulation in all areas of previous activity. One patient had significantly decreased activity on PET (4 weeks) later confirmed as PR by CT. Two patients have been retreated including one CRu (1 year) who showed renewed positive activity on PET imaging (negative CT) which returned to negative following retreatment and 1 PR. There have been no dose limiting toxicities seen to date on initial or retreatment. Time activity curves were generated after drawing ROIs and analyzed with SAAM II. Doses were calculated using MIRDOSE 3.1 (Stabin 1996). Deposited doses to critical organs were 0.48, 0.55, 2.13, 0.49, 0.37 cGy/mCi to the liver, lung, kidney, marrow and total body, respectively, and were significantly lower than those seen with the approved iodine labeled anti-CD20 monoclonal antibody (3.03, 2.92, 7.25, 2.41, 0.89 cGy/mCi for the same organs). LR131 demonstrated rapid clearance from blood and normal organs with retained activity in sites of tumor. Tumor deposited doses ranged from 45 cGy in the patient that did not target to 3600 cGy. CONCLUSION: LR131, at the administered doses studied to date, has been well tolerated with only mild to moderate reversible toxicity. LR131 has demonstrated targeting and clinical efficacy that has correlated with CT and PET imaging

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