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Table 6 Safety related findings of RNase treated laboratory models and cancer patients

From: Promises of eukaryotic ribonucleases for cancer treatment: a systematic review

No

Author, YYYY

RNase

Mol. Wt (kDa)

cell lines / in vivo

Method / Assay

Safety / toxicity

1

Mikulski et al., 2002 [22]

Ranpirnase

12

Phase II clinical trial on patients with unresectable Malignant Mesothelioma

Safety measurements (frequency of adverse events using physical, vital signs and laboratory evaluations)

- Sixteen (15.2%) of 105 patients were removed from the study because of adverse experiences (renal insufficiency, allergic reaction, proteinuria)

2

Vogelzang et al., 2001 [19]

Ranpirnase (Onc®)

12

Phase II clinical trial on patients with unresectable kidney cell carcinoma

Physical examinations, lab. analysis and adverse events of 14 patients were performed / recorded weekly

- No higher level toxicities occurred

- 5 patients with increased serum creatinine

- 1 patient with 4 + proteinuria

- Drug withheld in 1 hypersensitive patient

3

Fang et al., 2012

[34]

RNase MC2

14

BALB/c Nude mice bearing Hep G2 Liver cancer

In vivo: tumor dimension, tumor volume, body weight, tissue Immuno-histochemical staining

- No detectable toxicity

- No effects on body weight

- No toxicity to normal tissues

4

Skvor et al., 2006

[33]

WLN-RNase

27

human lymphocyte and athymic nude mice

Immunosuppressive activity and Spermatogenic toxicity analysis

- Low immunogenicity & embryotoxicity

- degenerative spermatogenic epithelium

- No allergic symptoms observed

5

Vasandani et al., 1999

[17]

Onconase

12

Apparently healthy mice

Kidneys examination using H&E tissue staining

- Proximal tubular toxicity was reversible after two weeks of treatment withdrawn

6

Laccetti et al., 1994

[12]

BS-RNase

14

- Fischer rat,

- 3LL Lewis Lung Carcinoma

- metastasis bearing mice

Heamatological tests, Physical & behavioral measurements, tumor & lung size measurement and H&E tissue staining

- No anemia & leukocytosis in treated tumor bearing animals

- No physical & behavioral changes in treated healthy animals

- No changes in hematologic tests in treated healthy animals

7

Joseph et al., 2020

[31]

Lp16-PSP

32

HeLa, HepG2, HL-60, HCT-15, SGC-7901, SKOV-3, HaCaT

Cell Counting Kit-8 (CCK-8)

- Higher selective cytoxicity i.e. IC50 of Lp16-PSP was lower in cancer cells than non-cancerous cells