Table S3. Clinical trials regarding immunotoxins

Conjugate

/ Clinical trial identifier / Drug / Target / Stage / Cancer / Effects
LMB-2 / NCT00967577
NCT00077922
NCT00080535
NCT00389506
NCT00321555
NCT00295958
NCT00085150
NCT00002765 / Pseudomonas Aeruginosa exotoxin (PE-38) / Tac (CD25) / Pilot study, I, II / ATL,
CLL,
CTCL,
HL,
HCL,
Metastatic Melanoma,
Pediatric Leukemias and Lymphomas / 1, 2
BL22 / NCT00126646
NCT00021983
NCT00074048
NCT00924040 / Pseudomonas Aeruginosa exotoxin (PE-38) / CD22 / I, II / CLL,
CD22+ Lymphomas / 3, 4
SS1(dsFv)-PE38 / NCT00066651
NCT00006981
NCT01041118
NCT01051934
NCT01362790 / Pseudomonas Aeruginosa exotoxin (PE-38) / Mesothelin / I / Cervical Cancer,
Fallopian Tube Cancer,
Head and Neck Cancer,
Lung Cancer,
Malignant Mesothelioma,
Ovarian Cancer,
Pancreatic Cancer,
Primary Peritoneal Cavity Cancer / 5, 6
LMB-9 / NCT00019435
NCT00005858 / Pseudomonas Aeruginosa exotoxin (PE-38) / Lewis Y / I / Bladder Cancer
Breast Cancer
Colorectal Cancer
Esophageal Cancer
Gastric Cancer
Lung Cancer
Pancreatic Cancer / 7
LMB-1 / NCT00001805 / Pseudomonas Aeruginosa exotoxin (PE-38) / Lewis Y / I / Breast Neoplasms
Colonic Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms / 8
MR1-1KDEL / NCT01009866 / Pseudomonas Aeruginosa exotoxin (PE-38) / EGFRvIII / I / Supratentorial Malignant Brain Tumor / Not yet available
CAT-8015 / NCT01030536
NCT01086644 / Pseudomonas Aeruginosa exotoxin (PE-38) / CD22 / I, II / NHL,
CLL / 3
RFT5-dgA / NCT00667017
NCT01378871
NCT00586547
NCT00586274 / deglycosylated ricin toxin A-chain (dgA) / CD25 / I, II / Relapsed/Refractory CTCL,
Relapsed/Refractory ATL/Lymphoma / 9-11
RFB4-SMPT-dgA / NCT00001271
NCT00007956 / deglycosylated ricin toxin A-chain (dgA) / CD22 / I / Refractory CD22 Positive B-Cell Lymphoma / 20
Denileukin diftitox / NCT00224354
NCT00357448
NCT00945269
NCT00425672
NCT00117845
NCT00003615 / Diphteria toxin (DT389) / CD25 / I, II / CLL,
Advanced Stage Ovarian Cancer,
Metastatic Melanoma,
Advanced Refractory Breast Cancer,
ATL,
Stage II, III, and IV Follicular Low-Grade NHL / 9-13
HuM-195/rGel / NCT00038051 / recombinant plant toxin gelonin (rGel) / CD33 / I / AML,
CMML,
Myeloproliferative Disorders,
Anemia, Refractory, With Excess of Blasts / 21
DT2219ARL / NCT00889408 / Diphteria toxin (DT389) / CD19, CD22 (bispecific antibody) / I / Leukemia,
Lymphoma / Not yet available
UCHT1 / NCT00611208 / Diphtheria toxin (catalytic and translocation domains) / CD3 / I, II / T-Cell Lymphomas,
T-Cell Leukemias,
Sezary Syndrome,
Mycosis Fungoides / 14
ABR-217620 / NCT00420888
NCT00132379
NCT00056537 / staphylococcal enterotoxin E / 5T4 / I, II, III / Advanced Renal Clear Cell Carcinoma,
Advanced Non-Small Cell Lung Cancer,
Pancreatic Cancer / 15,16
Denileukin diftitox / NCT00224354
NCT00357448
NCT00945269
NCT00425672
NCT00117845
NCT00003615 / Diphteria toxin (DT389) / CD25 / I, II / CLL,
Advanced Stage Ovarian Cancer,
Metastatic Melanoma,
Advanced Refractory Breast Cancer,
ATL,
Stage II, III, and IV Follicular Low-Grade NHL / 9-13
DT2219ARL / NCT00889408 / Diphteria toxin (DT389) / CD19, CD22 (bispecific antibody) / I / Leukemia,
Lymphoma / Not yet available
UCHT1 / NCT00611208 / Diphtheria toxin (catalytic and translocation domains) / CD3 / I, II / T-Cell Lymphomas,
T-Cell Leukemias,
Sezary Syndrome,
Mycosis Fungoides / 14
ABR-217620 / NCT00420888
NCT00132379
NCT00056537 / staphylococcal enterotoxin E / 5T4 / I, II, III / Advanced Renal Clear Cell Carcinoma,
Advanced Non-Small Cell Lung Cancer,
Pancreatic Cancer / 15,16

AML = Acute Myeloid Leukaemia; ATL = Adult T-Cell Leukaemia; CMML = Chronic Myelomonocytic Leukaemia; CLL = Chronic Lymphocytic Leukaemia; CTCL = Cutaneous T-Cell Lymphoma; HCL = Hairy Cell Leukaemia; HL = Hodgkin’s Lymphoma; NHL = Non-Hodgkin’s Lymphoma

References

1.Kreitman RJ, Fitzgerald DJ, Pastan I. Approach to the patient after relapse of hairy cell leukemia. Leuk Lymphoma. Oct 2009;50 Suppl 1:32-37.

2.Kreitman RJ, Wilson WH, White JD, et al. Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol. Apr 2000;18(8):1622-1636.

3.Kreitman RJ, Arons E, Stetler-Stevenson M, Fitzgerald DJ, Wilson WH, Pastan I. Recombinant immunotoxins and other therapies for relapsed/refractory hairy cell leukemia. Leuk Lymphoma. Jun 2011;52 Suppl 2:82-86.

4.Kreitman RJ, Squires DR, Stetler-Stevenson M, et al. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. Sep 20 2005;23(27):6719-6729.

5.Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I. Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin Cancer Res. Aug 15 2009;15(16):5274-5279.

6.Hassan R, Bullock S, Premkumar A, et al. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. Sep 1 2007;13(17):5144-5149.

7.Hausner PF, Karp JE, Edelma NL, et al. Phase I study of LMB-9 (B3(dsFv)PE38), a recombinant disulfide stabilized anti-Lewis Y immunotoxin ad- ministered by continuous infusion. Proc. Am. Soc. Clin. Oncol. 2003;122(abstract 736).

8.Hassan R, Williams-Gould J, Watson T, Pai-Scherf L, Pastan I. Pretreatment with rituximab does not inhibit the human immune response against the immunogenic protein LMB-1. Clin Cancer Res. Jan 1 2004;10(1 Pt 1):16-18.

9.Foss F, Demierre MF, DiVenuti G. A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. Jul 15 2005;106(2):454-457.

10.Kuzel TM, Li S, Eklund J, et al. Phase II study of denileukin diftitox for previously treated indolent non-Hodgkin lymphoma: final results of E1497. Leuk Lymphoma. Dec 2007;48(12):2397-2402.

11.Gerena-Lewis M, Crawford J, Bonomi P, et al. A Phase II trial of Denileukin Diftitox in patients with previously treated advanced non-small cell lung cancer. Am J Clin Oncol. Jun 2009;32(3):269-273.

12.Prince HM, Duvic M, Martin A, et al. Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol. Apr 10 2010;28(11):1870-1877.

13.Natarajan N, Telang S, Miller D, Chesney J. Novel immunotherapeutic agents and small molecule antagonists of signalling kinases for the treatment of metastatic melanoma. Drugs. Jul 9 2011;71(10):1233-1250.

14.Woo JH, Lee YJ, Neville DM, Frankel AE. Pharmacology of anti-CD3 diphtheria immunotoxin in CD3 positive T-cell lymphoma trials. Methods Mol Biol. 2010;651:157-175.

15.Borghaei H, Alpaugh K, Hedlund G, et al. Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer. J Clin Oncol. Sep 1 2009;27(25):4116-4123.

16.Robinson MK, Alpaugh RK, Borghaei H. Naptumomab estafenatox: a new immunoconjugate. Expert Opin Biol Ther. Feb 2010;10(2):273-279.

17.Castelletti D, Fracasso G, Righetti S, et al. A dominant linear B-cell epitope of ricin A-chain is the target of a neutralizing antibody response in Hodgkin's lymphoma patients treated with an anti-CD25 immunotoxin. Clin Exp Immunol. May 2004;136(2):365-372.

18.Schnell R, Borchmann P, Staak JO, et al. Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma. Ann Oncol. May 2003;14(5):729-736.

19.Schnell R, Vitetta E, Schindler J, et al. Treatment of refractory Hodgkin's lymphoma patients with an anti-CD25 ricin A-chain immunotoxin. Leukemia. Jan 2000;14(1):129-135.

20.Sausville EA, Headlee D, Stetler-Stevenson M, et al. Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. Blood. Jun 15 1995;85(12):3457-3465.

21.TargaTherapeutics. Human Clinical Trials Results with HuM195/rGel.

Table S3: Details of the clinical trials involving immunotoxins (data gathered from US clinicaltrials.gov, Clinical Trialsregister EU and available bibliography in sponsor an PubMed websites).